WELCOME TO

SEMINAR ON

QUALITATIVE and QUANTITATIVE DEPARTMENTAL LAYOUT OF STERILE

DOSAGE FORM

SHRI B.M.SHAH COLLEGE OF PHARMACEUTICLE

EDUCATION & REASEARCH , MODASA

GUIDED BY: Dr. M. R. PATELPrincipale & HOD in pharmaceutics

PRESENTEDE BY:SAHILHUSEN I . JETHARAM. PHARM – I (2013-14)ROLL NO. - 02

CONTENTS

Definition of sterile dosage form Type of sterile preparations

PARENTERALS INTRODUCTION COMPONETS of PARENTERAL DOSAGE FORMS QUALITATIVE DEPARTMENTAL LAYOUT Plant Layout Diagram of flow material Typical parenteral plant layout with space requirement Qualitative Layout Of Parentral Manufacturing (circular flow & parallel flow) Quntitative Departmental Layout

OPTHALMIC PREPARATION Definition Types Requirenments Simpler Flow Diagram Showing Arrangement Of Different Area

REFERANCES

Definition “Sterile dosage forms include parenteral (i.e. Solution, suspension etc. ,) , non parenteral (i.e. implant, ophthalmic etc.,) & irrigation preprations dosage forms.”

All the dosage forms should meet their standard requirements of purity, identity, sterility and stability.

When the term sterile dosage form is used, intrefers to a product of a general group of pharmaceuticals having in common the characteristic of sterility. i.e. freedom from living micro-organisms.

Sterility is a required characteristic of these pharmaceuticals because of the method, site, or rout of administration.

Sterile products are the dosage form of therapeutic agent that are free from viable micro-organisms.

Sterile - Absolute term as the state of freedom from all viable organism.

Type of sterile preparations(a). Parenteral preparations.

Parenterals are divided into two groups.(i). Small volume parenterals (volume less than 100 ml). (ii). Large volume parenterals (volume 100ml or more than 100ml).

(b). Ophthalmic preparations.(i). Eye drops(ii). Eye ointments

(c). Irrigation solutions.

(d). Dialysis solutions & allergenic extracts.

(e). Diagnostic agent (f). Surgicals

PARENTERALS

INTRODUCTION

Para: Beyond & Enteron: intestine i.e. beside the intestine.

These are preparations given by other than oral routes.

PARENTRAL PRODUCTS are sterile preparations intended to be administered by injection under or through one or more layers of skin or mucous membranes..

COMPONETS of PARENTERAL DOSAGE FORMS

1. Content(Formulations):

a. Therapeutic Agents : API

b. Vehicle(Solvent): Aq., Water miscible , Non-Aq.

c. Additives: Tonicity adjacent Preservative, Antimicrobial etc.

2. Container : Glass, Plastic(Thermoplastic)

3. Closure: Rubber ( Elastomer , Natural)

QUALITATIVE DEPARTMENTAL LAYOUTPRODUCTION FACILITIES:

Clean up area1.Garment ,container and shelving2.Seating bench3.Cleanroom computers4.Vacuum bachout rig5.CCD cryostat6.Monochromator7.Sputter coater8.Work bench9.Class 4 laser10.Work bench11.Laminar air flow cabinet12.Granite surface table13.Work bench14.Cleanroom table cabinet15.Cabinet16.Laminar flow cabinet17.Cabinet18.Work bench19.Work bench20.Optical allignment rig.

Entrance

FIRE EXIT FIRE EXIT

DARK CLEANROOM

WHITE CLEAN ROOM

ENTER ROOM

26

1.THE CLEAN UP AREA

QUALITIES OF CLEAN ROOM

The room should undergo 15-20 air changes per hour. HEPA filters are to clean the air entering the room. HEPA filters remove all airborne particles of size 0.3 or larger with an efficiency of 99.97%. Maintaining higher air pressure(+ve pressure) within the critical area to minimize infiltration

of airborne contaminants from outside. Care should be taken to ensure that air flows do not distribute particles from a particle-

generating person, operation or equipment to a zone of higher product risk. A warning system should be provided to indicate failure in the air supply.

Adjacent rooms of different grades should have a pressure differential of 10 - 15 Pascals. Counters in the clean room should be made of stainless steel or other nonporous, easily

cleaned material. Walls and floors should be free from cracks or crevices and have rounded corners. If the

walls or floors are to be painted, epoxy paint is used. The air flow should move with uniform velocity along parallel lines. The velocity of the air flow is 90 ± 20 ft/m3. Providing temp. & humidity controls appropriate to the product being manufactured.

2.THE COMPOUNDING AREA

3. Aseptic Production

HEPA filter, Laminar Air Flow, Class 100 Area.DOP test

.

B. APPROPRIATE UNIFORM FOR OPERATORS ENTERING IN ASEPTIC FILLING ROOMA. HORIZONTAL LAMINAR FLOW

•Clothing•PERSONNEL & GOWNING

A. LAMINAR AIR FLOW UNIT HEPA (HIGH EFFICIENCY PARTICULATE AIR filtration)

HEPA Filter HEPA filters are composed of a mat of randomly arranged fibers

(polyvinylidene fluoride -PVDF) Key metrics affecting function are fiber density and diameter, and filter

thickness

There are four basic mechanism in which fibrous air filter remove contamination from the air stream.

1. Straining or Sieving 2. Impaction 3. Interception 4. Diffusion

Laminar flow hoods: These are clean air work benches are specially designed to ensure the

aseptic preparation of sterile products. Laminar air flow hoods are generally used in conjunction with clean rooms.

For laminar air flow work station the air flow rates shall be 0.3 meter per second (vertical) and 0.45 (horizontal)

Introduction of personnel, equipment, and material into the work area provides sources of particulate matter which may contaminate the product.

Very small particles are not heavy enough to settle due only to the force of gravity, but instead are carried and directed by air currents. and if there is turbulent air, particles may be driven into product.

Laminar air flow velocity satisfactorily sweeps the area yet does not create unacceptable turbulence.

B. FILLING AREA :-

It is the most critical area in parenteral plant, where the product & sterilized components are exposed to room environment. Therefore these areas are specially constructed, filtered, and maintained to prevent environmental contamination.

Single filling area :-

MATER

IAL

FILLING AREA

EQUIPMENT PREPARATION

PR

OD

UC

T GOWNING AREA

PERSONAL

Multiple use filling Area:- Equipment

preparationFilling

Personal

Product

Equipment

MATERIALFilling

Filling

Filling

PERSONNEL & GOWNING No. of workers should kept to a minimum. Training of personal Personal hygiene:-All employees should be in good health, Subjected

to Physical examination, Understood their responsibilities to report own illness like cold, a sore throat, or other infection.

Clothing :- Uniform is made up of Dacron and Span polyethylene. Hats & masks are sometimes made of special parchment paper. Foot wears -plastic and rubber material.

Clean

Changing

area

Equipment & Component prepn

Area

Clean Filling Area

MaterialEntry

SolutionPrep.

Area

Clean

Changing

areaEquipment & Component prepn

Area

Comp.Entry

Clean Filling Area

TerminalSterilization

Unidirectional

Clean Zone

C. Layout for Terminal Sterilization

.

5.FINISHING or PACKAGING AREA4.THE QUARANTINE AREA

Final product is stored in the quarantine area until distributed

PLANT LAYOUT

Diagram of flow material

Typical parenteral plant layout with space

requirementFUNCTION Area

Square meter Percentage

Production 11,094 45.1

Warehouse 7,606 30.9

Administration 1,018 4.1

Utility 1,716 4.1

Quality control 1,716 7.0

Maintenance 1,014 4.5

Employee services

1,014 4.1

Security 39 0.9

Total 24,607 100.0

Total 150 M2 manufacturing area +100M2 ancillary for SVP or +150 M2 for LVP

PAPER 412/1 M.PHARM-I (2007-08) CHETAN GANDHI

QUALITATIVE LAYOUT OF PARENTERAL MANUFACTURING (circular flow)

PAPER 412/1 M.PHARM-I (2007-08) CHETAN GANDHI

QUALITATIVE LAYOUT OF PARENTERAL MANUFACTURING (parallel flow)

QUANTATIVE DEPARTMENTAL LAYOUT

PERSONNEL All employees should be

• in good health • Subjected to Physical examination• Understood their responsibilities to report own illness like cold, a sore

throat, or other infection. Personnel entering the aseptic areas should be required to follow a definite preparatory procedure. Uniform is made up of Dacron and Span polyethylene. →hats & masks are sometimes made of special parchment paper. personnel working in equipment wash rooms, (sterilizing rooms) & packaging areas are normally required to wear clean uniforms daily and to be conscious of cleanliness, but are not required to meet the special requirements for personnel entering the aseptic areas.

TYPE OF PRODUCTION LINE

Unitpackaging

Container

washing

Depyrogenation

Compounding

FillingTerminatedsterilization

Packaging Inspection

CONTINUOUS PRODUCTION LAYOUT

INTEGRATED PRODUCTION LINE

Unitpackaging

Container wash

Depyrogenation

Filling

Term

inal

Steril

izat

i

on

InspectionPackaging

PROCESSING

6 functional areas;1.Warehousing or Procurement2.Compounding area3.Material support area4.Aseptic filling area5.Packaging area6.Quarantine area

According to flow diagram

Warehousing or Procurement → Compounding area ↓Material support area → Aseptic filling area ↓

Packaging area ↓Quarantine area

DIFFERENT TYPE OF PRODUCTION LINE

Personnel

Gowning

Equip. Prep.FillingMaterial Product

Equip. Prep.

Equip. Prep.

Filling

Filling

Product

ProductMaterial

Gowning

Product

Fig; ASEPTIC FILLING AREA

Personnel

Gowning

Equip. Prep.

Material

Pro

duc

t

Filling

Filling

Filling

Filling

Equip. Prep.

Equip. Prep.

Equip. Prep.

Material

Material

Material

Material

Material

Equip. Prep.

Equipment

Product

Equip. Prep.Personnel

OPTHALMIC PREPARATION

Anatomy of eye

Definition:

Ophthalmics are defined as the dosage forms intended to be administered on to the external surface of the eye (known as topical preparations), inside (known as intraocular preparations) or adjacent to the eye (known as periocular preparations) or those used in combination with ocular appliances.

Ophthalmics are used therapeutically or prophylactically. Therapeutically useful in the treatment of intraocular or surface

conditions like conjunctivitis or inflammation, infections of the eye or eyelids etc.

Prophylactically useful in post surgical and post trauma preparations.

TYPES OF OPHTHALMIC DOSAGE FORM

1. Ophthalmic Solutions includes drops and lotions2. Ophthalmic Suspensions3. Ophthalmic Ointments4. Ophthalmic Emulsions5. Ophthalmic Gels6. Ophthalmic Gel-forming solutions7. Ophthalmic Injections8. Irrigation Solutions (Intraocular)9. Ocular Inserts10. Sterile Powders11. Contact Lenses Care Solutions

PAPER 910201/vijay/m.pharm-1/LMCP 352009-10

DOSAGE FORMS ADVANTAGES DISADVANTAGES1. Solutions -convenience -rapid corneal elimination.

-loss of drug by drainage.No sustained action

2. Suspensions -patient compliance-best of drug with slow dissolution

-drug properties decide performance.-loss of both solution & suspended solid.

3. Emulsions -prolonged release of drug from vehicle.-enhanced pulsed entry.

-patient non compliance.-Blurred vision-possible oil entrapment.

4. Ointments -Flexibility in drug choice-improved drug stability-increased tissue contact time.-inhibition of dilution by tears.

-sticking of eyelids.-poor patient compliance-blurred vision-no true sustained effect.

5. Gels -comfortable-less blurred vision than ointment.

-no rate control on diffusion.-matted eyelids after use.

6.Erodible inserts -effective-flexiblility in drug type & dissolution rate-need only be introduced into eye & not removed.

--patient discomfort-requires patient insertion-occasional product.

7. Non-erodible inserts -controlled rate of release-prolonged delivery-flexibility for type of drug selected.-sustained release

-patient discomfort-irritation to eye-tissue fibrosis

TYPES/CLASSES OF OPHTHALMIC DOSAGE FORMS :

REQUIREMENTS OF OPHTHALMIC PREPARATIONS

Clarity Isotonicity pH approximately equal to 7.4 (near to tear fluid) Purity and stability Sterility Viscosity Surface activity Preservation to prevent the growth of microorganisms

Sterile and particle-free. Iso-osmotic with the lachrymal secretion. Optimum viscosity

SIMPLER FLOW DIAGRAM SHOWING ARRANGEMENT OF DIFFERENT AREA

RAW MATERIAL

Highest quality When raw material are rendered sterile before manufacturing process,the

reactivity of raw material with sterilizing medium must be completely evaluated & sterilization must be validated.

In most sterile dasage form largest proportion is of “water” For the preparation intended for parenteral administration ,U.S.P. xxii

requires the use of →WFI → SWFI → BWFI

All of above are produced by distillation or reverse osmosis & circulation at relatively high temperature up to 800c, or alternatively its disposal at every 24 hrs, in all S.S. equipment of highest attainable , corrosion resistant quality

PROCESS FLOW CHART

REFERANCES

Pharmaceutical dosage forms (Parenteral Preparation) by Kenneth E. Avis, Leon Lachman, Vol-1.

Pharmaceutical dosage forms (Parenteral Preparation) by Kenneth E. Avis, Leon Lachman, Vol-2.

Drugs & Cosmetics Act 1940. The theory and Industrial pharmacy by Leon Lachman, Third edition Pharmaceutical science by Remington, 20th edition Pharmaceutical process Validation by Loftus & Nash: 29-90. Remington-The science and practice of pharmacy 21st edition volume I Good manufacturing practices for pharmaceuticals-A plan for total quality

control.Marcel Dekker www.getthatmag.com www.fabtecheng.com www.ahind.com www.nkambica.com Sterile Pharmaceutical Manufacturing by Groves Gisan

Ph. No. :- +918460378336Address:- 44, Assiyana Society; Dugarvada Road, Taluko & City : Modasa State: Gujarat Country: IndiaEmail: sahil.pharm4@gmail.com

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