If leak test fail during in process checks what needs to be done?

Immediately stop packing process and check for

    1. Sealing temperature,                 

    2. Verify for any possible changes like foil width, knurling etc.

    3. Check & quarantine the isolated quantity of packed goods from last passed         in-process.

    4. Collect random samples & do retest.

    5. Blisters from the leak test passed containers shall allow to go further and           rest must be deblistered/defoiled accordingly.

What is the formula for calculating number of air changes in an area?

Number of air changes/hour in an area is:- 

                   = Total Room Airflow In CFM x 60

                      Total Volume of room in cubic feet

For calculating Total Room Airflow in CFM, first calculate air flow of individual filter. 

Formula is given below.

Air flow (in cfm) = Avg.air velocity in feet/Minute x Effective area of filter                                                  

Then find Total air flow. The Formula is:-

Total Air flow = Sum of air flow of individual filter.

Air flow Velocity can be measured with the help of Anemometer.

What is the formula for calculating number of air changes in an area?

Number of air changes/hour in an area is

                   = Total Room Airflow In CFM x 60

                    Total Volume of room in cubic feet

For calculating Total Room Airflow in CFM, first calculate air flow of individual filter. Formula is given below.

Air flow (in cfm) = Avg.air velocity in feet/Minute x Effective area of filter                                                  

Then find Total air flow. Formula is

Total Air flow = Sum of air flow of individual filter.

Air flow Velocity can be measured with the help of Anemometer.

What is the formula for calculating number of air changes in an area?

Number of air changes/hour in an area is

                   = Total Room Airflow In CFM x 60

                    Total Volume of room in cubic feet

For calculating Total Room Airflow in CFM, first calculate air flow of individual filter. Formula is given below.

Air flow (in cfm) = Avg.air velocity in feet/Minute x Effective area of filter                                                  

Then find Total air flow. Formula is

Total Air flow = Sum of air flow of individual filter.

Air flow Velocity can be measured with the help of Anemometer.

What is the formula for calculating number of air changes in an area?

Number of air changes/hour in an area is

                   = Total Room Airflow In CFM x 60
                    Total Volume of room in cubic feet
For calculating Total Room Airflow in CFM, first calculate air flow of individual filter. Formula is given below.

Air flow (in cfm) = Avg.air velocity in feet/Minute x Effective area of filter                                                

Then find Total air flow. Formula is
Total Air flow = Sum of air flow of individual filter.

Air flow Velocity can be measured with the help of Anemometer.

What is the formula

What is the purpose of stress testing in stability studies?

Stress testing of the drug substance can help identify the likely degradation products, which can in turn help establish the degradation pathways and the intrinsic stability of the molecule and validate the stability indicating power of the analytical procedures used. The nature of the stress testing will depend on the individual drug substance and the type of drug product involved.

What countries comes under climatic zone ivb?

Brazil, Cuba, China, Brunei, Cambodia, Indonesia, Malaysia, Myanmar, Philippines, Singapore, Thailand

According to WHO guidelines what is the storage condition of climatic zone iva and zone ivb?

Zone IV a: 30°C and 65% RH (hot and humid countries)

Zone IV b: 30°C and 75% RH (hot and very humid countries)

Forced degradation( stress testing ) & accelerated stability testing are same?

Forced degradation and stress testing are not same. Stress testing is likely to be carried out on a single batch of the drug substance. The testing should include the effect of temperatures (in 10°C increments (e.g., 50°C, 60°C) above that for accelerated testing), humidity (e.g., 75 percent relative humidity or greater) where appropriate, oxidation, and photolysis on the drug substance. The testing should also evaluate the susceptibility of the drug substance to hydrolysis across a wide range of pH values when in solution or suspension. Photo stability testing should be an integral part of stress testing.

Water for pharmaceutical use shall be free from any cations, anions, heavy metals & any other impurities why?

   Water for pharmaceutical must be free from inorganic as well as organic impurities, minerals, and heavy metals. Some impurities like calcium, magnesium, ferrous are responsible for degradation of drug molecule, many cations like ferrous and calcium magnesium act as catalysts in degradation reaction of drug molecule, anions like chloride are highly active they participate in nucliophylic substitution reactions, where in they break a double bond between -C=C- in to a single bond as CL –CH-CH2- , which a reason why we observe that color dies tend to fed in presence of chlorine as most of the dies used are diazo compounds which has plenty of places for nucliophylic substitution reactions, which is also a reason why stability of drug is drastically affected in presence of cations and anions from mineral origin present in water.

    Heavy metals like lead and arsenic are highly cumulative neurotoxic metals, heavy metals are not eliminated out of our body easily like other drugs and molecules but heavy metals bind with proteins and tend to get accumulated in fatty tissues, nerve tissue is most likely to get damaged by heavy metals, heavy metal causes nervous tissue damage there for water must be free from heavy metals.

Why water for pharmaceutical use is always kept in close loop in continuous circulation?

Water is very important & essential medium for any pharmaceutical preparation. So this use very carefully.

      Water is a best medium for most microorganisms, microorganism can be a highly pathogenic which causes serious diseases(many diseases are  water born), these pathogens infect after consumption of contaminated water, microorganisms tend to settle on a surface if water is allowed to stand in a stagnant position for few hours, these settled microorganism form a film over the surface of vessel and piping, such film formed by microorganisms is also called as bio-film, bio-films are very difficult of remove, once a bio-film is formed at a particular point then that point may form a bio-film again even after cleaning very easily as seed from this point is may not completely get removed effectively.

   Bio-films then can become a source of microbial contamination's, therefore purified water after collection in a distribution system is always kept in a closed loop in a continuous circulation.

      A continuous circulation is also not enough at some points, therefore it is aided with high temperature range from 65 °C to 80°C, a minimum temperature of 65 °C is considered a self sanitizing, but better assurance is obtained with a temperature of 80°C.

      Purified water collected should be stored in a stainless still vessel which must facilitate distribution to the point of use in a closed loop of continuous circulation, tank should be made of corrosion free material of construction, and must facilitate sanitization and easy cleaning. Thank's

Difference between Karl Fischer Titrator and Loss on drying (LOD).

Actually Karl Fischer titration and loss on drying (LOD) are the methods, which is used for determining moisture content in a product. We detect LOD by moisture analyzer machine.

Karl Fischer Titrator:  KF is a method, which measures only the water content (i.e. it's water-specific) in a product sample. Karl Fischer titration is a chemical method. It involves adding a reagent to the sample to cause a reaction that converts the water in a product to a non-conductive chemical.

Karl Fischer Titrator

LOD-Loss On Drying: LOD that means loss on drying we determine lod by the moisture analyzer machine, lod measures the total change in weight of a material as a result of drying. For some products, components such as alcohol or fat evaporate with the water. Therefore, the LOD method measures both the water and volatile impurities such as those mentioned previously Loss on Drying compares the weight of a product before and after it is dried. This difference in weight is taken as the percentage of moisture in the product.

Moisture Analyzer 

Finally, we can say by the Karl Fischer Titrator we only detect what amount of water into the substance, but by the moisture analyzer we can not detect what amount of water like any other liquid substance into the materials. So here we detect what percentage of any kind liquid present into the materials. 

For Example: (LOD-Loss On Drying) Suppose 50 gm materials used in moisture analyzer machine after drying determine how percentage weight loss of this 50 gm materials, so we say loss on drying.   

IPC/IPQC - In Process Control-Its importance in Pharmaceutical Industry.

In a pharmaceutical Industry in process check is very important subject and this also a part of quality assurance department. So we may say QA department is the father of every manufacturing Company.... here i describe about IPC.........

In-Process Control refers to the checks performed during an activity (it can be manufacturing or packing) in order to monitor and if necessary to adjust the process and/or to ensure that the intermediate or finished product conforms to its specification. The control of equipment and environment may also be regarded as the part of in process control.

In process checks are vital as manufacturing activity itself and the same shall be performed at regular intervals. Frequency of the in process checks need to be realistic. By carrying out in process checks one can assure the product quality.

In process quality check is designed to provide early warning for quality or other problems arising during production. In Other words it is intended to provide a snap shot of the quality of the product manufactured at the factory. The objective of in process checks are both quality control and process control.

In process checks shall include following process controls:-

l    # Measured values obtained from process equipment. e.g. Inlet & outlet temperature of FBD

l    # Measured values obtained from persons e.g. Times

l    # Product attributes e.g.Weight,Hardness,friability

l    # Measured values obtained from the room environment e.g. Temperature, Humidity.

Note: Rejected in process materials should be identified and controlled under a quarantine system designed to prevent their use in manufacturing.

During process checks following things needs to be checked:-

l    # Verification of the status labels on the area, equipment's  & process containers.

l    # Online stage wise review of the batch record (Online review).

l    # Cleanliness of the area, equipment and line clearance.

l    # Confirming material correctness, AR.no, quantity & vendor against the batch record.

l    # Product attributes like weight variation, avg.wt, hardness, thickness, D.T, friability.

l       Monitoring environmental conditions.

l    # Weight of the blend & other intermediates.

l    # Checking the appearance tablet during compression & coating

l    # Solution preparation.

l    # Film formation and integrity.

l    # Ensure machine setting parameters match with batch records.

l    # Yield verification of various stages of production

l    # Sampling

In Process Checks During Manufacturing:-

l    # Ensure correct materials are brought in for manufacturing activity.

l    # Check sieve integrity.

l    # Ensure manufacturing is carried out as per the instruction given in the BMR.

l    # Ensure operators are wearing hand gloves and nose mask during all stages of manufacturing.

l    # Verify the records for online entries.

l    # Environmental Monitoring.

l    # Check & verify equipment parameters like temperature, drying time etc.

l    # Checking process parameters like Appearance,Avg.Weight,Group Weight,Hardness,friability,       DT etc.

l    # Yield verification.

l    # Checking the weights of in process materials.

l    # Checking labeling status of the quarantine materials.

l    # Ensure doors are closed during processing.

In Process Checks During packing:-

l    # Ensure Name, Strength, Volume & quantity is correct.

l    # Check the status labels on equipment, area & in process container.

l    # Over printing quality.

l    # Batch coding details on primary & secondary pack (B.No.,Mfg.,Exp., M.R.P.etc.).

l    # Text matter on the ptd. foil & carton.

l    # Verification forming & sealing temperature.

l    # Ensure blisters are free from knurling defects.

l    # Leak Test.

l    # Pharmacopeial status of the material used is correct.

l    # Mfg.License number is printed correctly.

l    # Preprinted packing materials provide mandatory information & legal status.

l    # Storage conditions details available in the packaging materials.

l    # Directions for use details available in the packaging materials.

l    # Ensure warnings against wrong administration is provided in the pack.

l    # Storage condition is same all printed packing Materials.

l    # Ensure correct leaflet is used for the product.

l    # Verify printed matter on the outer cartons and shippers.

l    # Ensure checkers are performing their activity in a proper way.

l    # Verify blisters & strips for alignment defects & empty pockets.

l    # Ensure doors are closed during processing.

l    # Verify the records for online entries.

l    # Environmental Monitoring.

l    # Sampling

Documentation:-

Results of the in process checks shall be documented with initials of the person carrying them out and results obtained. If problems or deviations from the manufacturing formula and processing instructions occurred, all relevant information associated to this have to be documented well.

Thank You 

Granulation and it's importance in tablet manufacturing process..

 GRANULATION & IT’S IMPORTANCE IN TABLET MANUFACTURING PROCESS

Granulation process is an inevitable step in tablet manufacturing as it improves flow property and compressibility of powder mass intended for compression. Granulation prevents segregation of the constituents of the powder mix.

Granulation is the process in which primary powder particles are made to adhere to form larger, multi particle entities called granules. Pharmaceutical granules typically have a size range between 0.2 and 4.0 mm, depending on their subsequent use.

Granulation is so important in tablet manufacturing process because it:-

1. Improve fluidity

2. Decrease segregation of the powder components

3. Decrease dusting

4. Improve compressibility of the material

An ideal granulation will contain all the constituents of the mix in the correct proportion in each granule, and segregation of the ingredients will not occur.

Types of granulation

Basically two types of granulation technique, but also other technique is direct compression 

1.Dry granulation   2. Wet Granulation

N.B: Wet granulation mostly used in tableting process, but this also depend on that chemical nature which we used for tableting.....

Dry granulation

In dry granulation the primary powder particles are aggregated under high pressure. There are two main processes. Either a large tablet (known as a ‘slug’) is produced in a heavy-duty tableting press (a process known as ‘slugging’) or the powder is squeezed between two rollers to produce a sheet of material (‘roller compaction’).

In both cases these intermediate products are broken using a suitable milling technique to produce granular material, which is usually sieved to separate the desired size fraction. Dry granulation technique is applicable  for drugs which do not compress well after wet granulation, or those which are sensitive to moisture.

Wet granulation

Wet granulation involves the massing of a mix of dry primary powder particles using a granulating fluid. The fluid contains a solvent which must be volatile so that it can be removed by drying, and be non-toxic. Typical liquids include water, ethanol and isopropanol, either alone or in combination. The granulation liquid may be used alone or, more usually, as a solvent containing a dissolved adhesive (also referred to as a binder or binding agent) which is used to ensure particle adhesion once the granule is dry. Water is commonly used for economical and ecological reasons. Its disadvantages as a solvent are that it may adversely affect drug stability, causing hydrolysis of susceptible products, and it needs a longer drying time than do organic solvents. This increases the length of the process and again may affect stability because of the extended exposure to heat. The primary advantage of water is that it is non-flammable, which means that expensive safety precautions such as the use of flameproof equipment need not be taken. Organic solvents are used when water-sensitive drugs are processed, as an alternative to dry granulation, or when a rapid drying time is required. In the traditional wet granulation method the wet mass is forced through a sieve to produce wet granules which are then dried. A subsequent screening stage breaks agglomerates of granules and removes the fine material, which can than be recycled. Variations of this traditional method depend on the equipment used, but the general principle of initial particle aggregation using a liquid remains in all of  the processes.

Glossary of Terms

Compressibility – Compressibility is the ability of powder to decrease in volume under pressure.

Important abbreviations need to know every pharmacy students

ABBREVIATIONS FREQUENTLY USED IN PHARMACEUTICALS

N.B: Probably Most used terms may green color 

AHU: Air Handling Unit 

AQL: Acceptable Quality Level

API: Active Pharmaceutical Ingredients

GLP: Good Laboratories Practice

ICH: International Conference on Harmonization

ISO: International Standard Organization/ International Organization for Standardization

GMP: Good Manufacturing Practice

cGMP: Current Good Manufacturing Practice

TQM: Total Quality Management

WHO:  World Health Organization

WHA: World Health Assembly

BMR: Batch Manufacturing Records

BPR: Batch Packaging Records

FDA: Food and Drug Administration

FD & C: Food, Drug and Cosmetics

IPC: In-Process Control/ Check

CBA: Collective Bargaining Agent

MCA: Medicines Control Agency (Britain)

MCC: Medicine Control Council (Africa)

ICRS:  International Chemical Reference Substances 

IRO: Industrial Relations Ordinance

EEC:  European Commission;

ISO/TC: International Organization for Standardization Technical Committee

PDCA: Plan, Do, Check, Act

PIC: Pharmaceutical Inspection Convention

PIC/S: Pharmaceutical Inspection Co-operation Scheme

DQ: Design Qualification

IQ: Installation Qualification

OQ: Operational Qualification

PQ: Performance Qualification

ASL: Approved Suppliers’ List

VMP: Validation Master Plan

TRS: Technical Report Series

CRS: Chemical Reference Substances

HEPA: High Efficiency Particulate Air

SAL: Sterility Assurance Level

IU: International Unit

IUPAC: International Union of Pure and Applied Chemistry

ANOVA: Analysis of Variance

HEPA: High Efficiency Particulate Air

HPLC: High Performance Liquid Chromatography

ICDRA: International Conference of Drug Regulatory Authorities

TLC: Thin Layer Chromatography

GC: Gas Chromatography

PVC: Poly Vinyl Chloride

PVDC: Poly Vinyledene Chloride

ROPP: Rolled on Pilfer Proof

RCC: Reinforced concrete

FTIR: Fourier Transform Infrared spectroscopy 

LAL: Limulus Amebocyte Lysate

RO: Reverse Osmosis

WFI: Water for Injection

FIFO: First-in-first-Out

FEFO: First Expired, First Out

EEFO: Earliest Expiry, First Out

HACCP: Hazard Analysis and Critical Control Point

FIP: International Pharmaceutical Federation

INN: International Non-proprietary Names

IFPMA: International Federation of Pharmaceutical Manufacturers Associations

IPEC: International Pharmaceutical Excipients Council

UNICEF: United Nations Children’s Fund

WTO: World Trade Organization

PDG: Pharmacopoeial Discussion Group

GTDP: Good trade and distribution practice

DAR: Drug Administration Registration           

DMF: Drug Master File                                    

DRA: Drug Regulatory Authority

EOI: Expression of Interest

ILO: International Labor Organization

NPS: Nonpareil seed

EDM: Essential Drugs and Medicines

BAN: British Approved Names

USAN: United States Accepted Names

GSP: Good storage practice

   MOA: Method of analysis

COA: Certificate of analysis

UNAIDS: United Nations Programme on HIV/AIDS

UNFPA: United Nations Population Fund

ASEAN: Association of South Asian Nations

TPN: Total Parenteral Nutrition       

BFS: Blow, Fill, Seal Technique (Ampule Filling)

LDPE: Low Density Polyethylene

HDPE: High Density Polyethylene

PP: Polypropylene

HVAC: Heat, Ventilation and Air conditioning

PPIC: Production Planning & Inventory Control

PPI: Proton Pump Inhibitor            

o. d.: Once daily

b. i. d.: Twice daily

TOC: Total Organic Carbon

t. i. d.: Thrice daily

q. i. d.: Four times daily

PMN: Phenylmercuric Nitrate

PMA: Phenylmercuric Acetate

BAC:  Benzalkonium Chloride

PVDC: Polyvinylidene Chloride

NE: Not Established

PET: Polyethylene Terephthalate

FAO: Food and Agriculture Organization

EEC: European Commission

USAID: U.S. Agency for International Development

ICDDRB: International Centre for Diarrhoeal Disease Research, Bangladesh

IBC: Intermediate Bulk Container

AAS: Atomic Absorption Spectroscopy

ICP: Inductively Coupled Spectroscopy

IC: Ion Chromatography

TGA: Therapeutic Goods Agency (Australia)

MHRA: Medicines and Healthcare products Regulatory Agency (UK)

Pharmaceutical Equipments

Here i describe mostly used Pharmaceutical Equipment such as Production equipment, Quality control equipment specially which is very important necessary equipment i just try to describe for the newly pharmacy student.......so try to read and try to understand any publishing article........

Why some medicine come in capsule form?

  Some medications come in capsule form, because the nature of the substance makes it difficult or impossible to manufacture in a tablet form. Creating a tablet requires finding a binding material that allows the medication to be formed into a solid shape but that does not affect its chemical composition nor its bio-availability. For example, the typical aspirin tablet is held together mostly by corn starch.

  Some medications come in capsule form, because many consumers have a distinct preference for capsules. Many consumers perceive capsules as easier to swallow. Some consumers perceive capsules as more effective.

   An interesting example of the preference for capsules is provided by a study ("Effect of Shape of Medication in Treatment of Anxiety States") published in 1972 in the British Journal of Psychiatry by psychiatrist M. Z. Hussain, who found that patients being treated for anxiety responded better to treatment with the same drug (chlordiazepoxide) in capsule form rather than tablet form. There is no known medical reason for this, but its psychological significance is compelling. Capsules have been the required form for most clinical trials of psychiatric medications since 1972.

  Also some reason in capsule form because:-

       1. The nature of chemical substance. 

       2. Rapid bio availability rather than tablet.

       3. Easy to swallow for older and child patient. 

       4. Easy to manufacture where tablet need to more step.

Difference between relative humidity and humidity.

This is very important thing for the pharmaceuticals also any other organization, so need to know difference between this..

       "Humidity" and "Relative Humidity" are not the same thing. Humidity means amount of water vapor present in air with respect to total amount of air.         Relative Humidity is the amount of moisture in the air 'relative' to the temperature (i.e. relative humidity is the amount of moisture in the air compared to what the air can "hold" at that temperature. When the air can't "hold" all the moisture, then it condenses as dew).

          The relative humidity is a measure of the amount of water vapor in the air (at a specific temperature) compared to the maximum amount of water vapor air could hold at that temperature, and is given as a percentage value. Relative humidity depends on the temperature of the air.

Seek for Quality Control Department...

FnF Pharmaceuticals Ltd.

Rautail, Nagarbathan, Jhenidah.

Who are interested to doing job in this Organization, send your updated CV attached with recent passport size photograph bellow this contact address:-

Working Station: Quality Control ( Factory ),  Jhenidah

Prefer: Candidates in this region.( Khulna Division ) 

email: lelinfnfpharma@gmail.com

P.N: 01740601602/ 01925684674   

Some common excipient, those are mostly used in pharmaceutical preparation.

Binders: To add cohesiveness to powder providing necessary bonding  to form granules

        Ex: CMC, Starch paste, Povidone, Avicel.

     N.B: Some binders soluble in non aq. system(like ethanol)for moisture sensitive drugs(ranitidine)

 Diluent: Increase physical size of the tablet in order to compressed the tablet.

              Ex: Starch, Lactose

Disintegrant: Agents added prior to granulation or during lubrication step or both process step

               Ex: Maize Starch, Lactose, Micro Crystalline Cellulose

Lubricants: Reduce the friction between the granules and die wall during compression and ejection

Ex: Water insoluble lubricant Mg,Na,Ca- stearate, Talk, Water soluble lubricant Na-acetate, Na-lauryl sulphate

     

   N.B: Mg-stearate boundary type lubricant form a coat around the individuals particles (Granules) which  remain  more or less intact during compression. Water insoluble lubricant More effective  as they used in low concentration, Water soluble lubricant must be used when the tablet must completely water soluble like effervescent tablet. Powder lubricant not used prior to wet granulation

Anti-adherent: Prevent sticking granules to the punch and to a laser extent to die wall

              Ex: Talk, Aerosil/Cabosil

Glidants: Improves flow characteristics  of the granules

              Ex: Talk , Starch, Aerosil

Colarant: To identify similar looking products within products line, Minimize possibility of mixture during manufacture.

           Ex: Dyes (water soluble), lakes (formed by adsorption of H2O soluble dyes on a hydrous oxide Al(OH)3 which result H2O insoluble dye)

             N.B: H2O soluble dyes are dissolve in the granulation system which                   assure uniform distribution

Adsorbent: Capable of holding up to 50% of its weight of water.

              Ex: Syloid, cab-o-sil/aerosol, Bentonite, Kaolin, Mg-silicate  

Choice of excepients: Depends on tablet type, desired characteristics, manufacturing process used and physical and chemical compatibility with API

Avicel: Micro-crystalline cellulose.

TYPE:

Grade	Size Micro meter	LOD
PH-101	50	4%
PH-102	90	4%
PH-105	20	3%
PH-200	180	4%
PH-302	90	4%

N.B: Generally PH-101 are mostly used in Wet Granulation, PH-102 are used in Direct Compression 

In expensive filler:

Ex: Encompress: Dibasic-Ca-phosphate, 

      Compactrol/Terra alba: Dihydrate Ca-sulphate

      Tritab: Tri-Ca-phosphate

Cellulose: Special grade of microcrystalline cellulose, have superior compressibility and high dilution potential for this properties good for formulation of small size tablets with high content of API.