Pharmaceutical Quality Control

Quality

Quality is the totality of features and characteristics of a products or service that bear on its ability to satisfy stated or implied needs.

Criteria for quality

⇨ Safety

⇨ Potency

⇨ Efficacy

⇨ Stability

⇨ Acceptability

⇨ Regulatory compliance

Five basic points for quality:

⇨ Safety

⇨ Quality

⇨ Identity

⇨ Potency

⇨ Purity

Quality control

It is the operational techques and activities that are used to fulfill requirements for quality.

Quality control= Testing + Assessment

Sampling

The process of taking a small portion from a lot/batch for test and analysis.

Sampling plans for starting materials

1. The n plan:

If number of containers are less than 5, then take a sample from each container.

If number of containers are more than 5, then take a sample from (√n + 1) container.

2. The p plan:

The p plan is based on the formula p = 0.4 ÷ N (N is the number of sampling units)

3. The r plan:

⇨ The r plan may be used when the material is suspected to be non-uniform and/or is received from a source that is not well known.

This plan is based on the formula r = 1.5 ÷ N, where N is the number of sampling units.

Quality Control Instruments

⇨ HPLC

⇨ UPLC

⇨ GC

⇨ AAS

⇨ TOC

⇨ FTIR

⇨ Particle size Analyzer

⇨ UV-visible spectrophotometer

⇨ Autoclave

⇨ Fume hood

⇨ Incubator

⇨ Melting point apparatus

⇨ Incubator

⇨ Dissolilution Tester

⇨ Disintegration Tester

⇨ Hardness Tester

⇨ Friability Tester

⇨ pH Meter

⇨ Conductivity Meter

⇨ Centrifuge Machine

⇨ Shieve Shaker

⇨ Density Tester

⇨ Polarimeter

⇨ Osmometer

⇨ Viscometer

⇨ Potentiometer

⇨ Karl Fisher Titrator

⇨ Flame Photometer

⇨ TLC

Quality Control vs Quality Assurance

⇨ Quality control is the operational technique and activities that are used to fulfill requirements for quality.

⇨ Quality assurance is a planned and systematic set of activities necessary to provide adequate confidence that a product or service will satisfy given requirements for quality.

⇨ QC = Test + Assessment

⇨ QA = Product design + GMP + QC + Quality goal activites

⇨ QC is the responsibility of the tester.

⇨ QA is the responsibility of the entire team.

⇨ QC implements the process.

⇨ QA helps to establish the process.

⇨ QC improves the development of a specific products service.

⇨ QA improves the process that is applied to multiple products that will ever be produced by a process.

Calibration

Calibration is a process of configuring an instrument to provide a result for a sample within an acceptable range. Calibration is a process that compares a known against an unknown. Calibration means system performance checking. Calibration is a tool to ensure that the instrument or equipment is working well. Calibration is done to nullify or remove the deviation by comparing with known or reference standard. Calibration is done to ensure that system is ready to use for any analysis. 

Purpose of calibration:

⇨ Performance checking of an instrument.

⇨ To ensure that the measuring accuracy is known over whole measurement range under specified environmental conditions for calibration.

Calibration vs Validation

⇨ Calibration is a process that compares a known against an unknown.

⇨ A validation is a detailed process of confirming that the instrument is installed correctly, that it is operating effectively, that it is performing without error.

⇨ Calibration means system performance checking.

⇨ Validation means method of analysis performance checking.

⇨ Calibration is a tool to ensure that the instrument or equipment is working well.

⇨ Validation is a tool to ensure that the analytical method is working well.

Spectroscopy

⇨ Atomic Absorption Spectroscopy

⇨ IR spectroscopy

⇨ Fourier transform Infra-red Spectroscopy

⇨ Nuclear Magnetic Spectroscopy

⇨ UV-visible spectroscopy

Atomic Absorption Spectroscopy (AAS)

Atomic absorption spectroscopy is a spectro-analytical procedure for the quantitative determination of chemical elements employing the absorption of optical radiation by free atoms in the gaseous state. 

AAS can be used to determine over 70 different elements in solution or directly in solid samples.

Main functions of AAS

⇨ Quantitative determination chemical elements

⇨ Metal Identification

Infrared (IR) Spectroscopy

Infrared spectroscopy is the spectroscopy that deals with Infrared region of the electromagnetic spectrum, that is light with a logner wavelenth and lower frequency than visible light. It covers a range of techniques, mostly based on absorption spectroscopy.

Principle of Infrared Spectroscopy:

Infrared spectroscopy exploits that molecules absorb specific frequencies that are characteristic of their structure. These absorptions are resonant frequencies, i.e. the frequency of the absorbed radiation matches the transition energy of the bond or group that vibrates. The energies are determined by the shape of the molecular potential energy surfaces, the masses of the atoms, and the associated vibronic coupling.

In particular, in the Born-Oppenheimer and harmonic approximations, i.e. when the molecular Hamiltonian corresponding to the electronic ground state can be approximated by a harmonic oscilator in the neighborhood of the equilibrium molecular geometry, the resonant frequencies are associated with the normal modes corresponding to the molecular ground state potential energy surface. The resonant frequencies are also related to the strength of the bond and the mass of the atoms at either end of it. Thus, frequency of the vibrations is associated with a particular normal mode of motion and a particular bond type.

Main function of IR Spectroscopy

⇨ It can rapidly measure the critical material attributes of a product in real time.

⇨ Determination of functional group and structural elucidation

⇨ Identify interaction between API and Excipients

⇨ Detection of Impurities

Fourier Transform Infrared Spectroscopy (FTIR)

FTIR spectroscopy is a measurement technique that allows one to record infrared spectra. Infrared light is guided through an interferometer and then through the sample (vice versa). A moving mirror inside the apparatus alters the distribution of infrared light that passes through the interferometer. The signal directly recorded, called an " Interferogram", represents light output as a functiom of mirtor position. A data-processing technique calked Fourier yransform turns this raw data into the desired result.

Main functions of FTIR:

⇨Identification of Molecular Structure of nano materials

⇨ Used to investigate various nano materials and proteins in hydrophobic membrane environment.

⇨ Evaluation of raw material and final product analyses prior to inspection and market release.

Main functions of NMR:

⇨ Determine Molecular structure at the atomic level of a sample

⇨ Identification of binding site, chemical reaction speed, molecular mobility, interatomic distance

⇨ Determine phase change, conformational & configurational alteration, solubility, diffusion potential

UV visible Spectroscopy

Ultraviolet-visible spectroscopy or ultraviolet-visible spectrophotometry refers to absorption spectroscopy or reflectance spectroscopy in the ultraviolet visible spectral region. This means it uses light in the visible and adjacent ranges.

Principle of Ultraviolet-Visible Spectroscopy

Absorption molecules containing pi-electrons or non-bonding electrons can absorb the energy in the form of ultraviolet or visible light to excite these electrons to higher anti-bonding molecular orbitals. The more easily excited the electrons, the longer the wavelength of light it can absorb.

Lambert's Law:

This law relates the absorptive capacity to the thickness of the absorbing medium. According to this law: "When a monochromatic radiation or light passes through a homogenous transparent medium, the rate of decrease of intensity of radiation with the thickness of the absorbing medium is directly proportional to the intensity of the incident light."

Beer's Law:

Absorption of light passes through a solution is proportional to the concentration of drug in the solution. According to the law: "When a monochromatic radiation or light passes through a homogenous concentration medium, the rate of decrease of intensity of radiation with the concentration of the solute in that system is directly proportional to the intensity of the incident light."

Beer-Lambert Law:

The Beer-Lambert law states that "The absorbance of a solution is directly proportional to the concentration of the absorbing species in the solution and the path length."

Thus, for a fixed path length, UV spectroscopy can be used to determine the concentration of the absober in a solution. It is necessary to know how quickly the absorbance changes with concentration.

Limitations of Beer-Lamber Law:

The linearity of the Beer-Lambert law is limited by chemical and instrumental factors. Causes of non-linearity include:

⇨ Deviations in absorptivity at high concentrations (>0.01 M) due to electrostatic interactions between molecules in close proximity.

⇨ Interaction with solvent: Hydrogent bondig

⇨ Scattering of light due to particulates in the sample.

⇨ Changes in Refractive index at high analyte concentration.

⇨ Shifts in chemical equilibria as a function of concentration

⇨ Non-monochromatic radiation

Deviations can be minimized by using a relatively flat part of the absorption spectrum such as the maximum of an absorption band stray light.

UV-visible Spectrophotometer:

A spectrophotometer is employed to measure the amount of light that a sample absorbs. The instrument operates by passing a beam of light through a sample and measuring the intensity of light reaching a detector.

Function of UV-Visible Spectrophotometer:

⇨ Absorbance detection

⇨ Measuring intensity of light by passing through the sample

⇨ Quantitative determination of impurites, transition metal ions, unknown compounds, highly conjugated organic compounds, 

⇨ Examine drug identity, purity, drug crystalline structures, interaction between active ingredients and excipients.

Resonance:

A signal in the spectrum is referred to as a resonance.

Chemical shift:

The frequency of a signal that means the frequency of the resonance is known as chemical shift.

Bathochromic Shift (Red Shift):

Bathochromic shift is a change of spectral band position in the absorption, reflectance, transmittance & emission spectrum of a molecule to a longer wavelength (Lower frequency). It is also called Red Shift.

Hypsochromic shift (Blue Shift):

Hypsochromic shift is a change of spectral band position in the absorption, reflectance, transmittance & emission spectrum of a molecule to a shorter wavelength (Higher frequency). It is also called Blue shift.

Chromophore:

Chromophore is a part of a molecule responsible for its colour.

eg, Nitro group, Carboxy group etc.

Auxochrome:

A auxochrome is a functional group of atoms with one or more lone pairs of electrons within attached to a chromophore alter both the wavelength and intensity of absorption.

Auxochrome is a colour enhancer group.

Auxochrome itself does not produce colour but enhance the colour of chromophore when attached with chromophore.

Conductivity meter

An electrical conductivity meter measures the electrical conductivity in a solution.  

It is commonly used in hydroponics, aquaculture and freshwater systems to monitor the amount of nutrients, salts or impurities in the water.

Functions of Conductivity meter:

By measuring electrical conductivity in a solution monitor the amount of nutrients, salts or impurities in the water.

Chromatography

Chromatography is the collective term for a set of laboratory techniques for the separation of mixtures. Chromatography is an analytical method by which the compounds are phydically separated prior to management. The main purpose of chromatography is to separate and quantify the target sample in the matrix. There are four main types of chromatography:

1) Liquid Chromatography (LC)

2) Gas Chromatography (GC)

3) Thin-Layer Chromatography (TLC)

4) Paper Chromatography (PC)

Thin Layer Chromatography (TLC)

Thin-Layer Chromatography is a chromatographic technique used to separate non-volatile mixture. Thin Layer chromatography is performed on a sheet of glass, plastic, or aluminium foil, which is coated with a thin layer of adsorbent material, usually silica gel, aluminum oxide or cellulose. This layer of adsorbent is known as the stationary phase.

After the sample has been applied on the plate, a solvent or solvent mixture, known as the mobile phase, is drawn up the plate via capillary action. Because of different analytes ascend the TLC plate at different rates, separation is achieved.

Thin Layer Chromatography can be used to monitor the progress of a reaction, identify compounds present in a given mixture, and determine the purity of substance. Specific examples of these applications include:

⇨ Analyzing ceramics and fatty acids

⇨ Detection of pesticides or insecticides in food and water

⇨ Analyzing the dye composition of fibers in forensics

⇨ Assaying the radiochemical purity of radiopharmaceuticals

⇨ Identification of Medicinal plants and their constituents.

Functions of TLC:

⇨ Used to separate non-volatile mixtures.

Liquid Chromatography

Liquid chromatography is used to test water samples to look for pollution in lakes and rivers. It is used to analyze metal ions and organic compounds in solutions. Liquid chromatography uses liquids which may incorporate hydrophilic, insoluble molecules.

HPLC (High Performace Liquid Chromatography)

HPLC is really the automation of traditional liquid chromatography under conditions which provide for enhanced separations during shorter periods of time.

Basic Principle of HPLC:

HPLC is a technique in analytical chemistry used to separate the components in a mixture, to identify each component, and to quantify each component. It relies on pumps to pass a pressurised liquid solvent containing the sample mixture through a column filled with a solid adsorbent material. Each component in the sample interfare slightly differently with the adsorbent material, causing different flow rates for the different components and leading to the separation of the components as they flow out the column.

Application of HPLC

⇨ Used to analyse finished drug products and their ingredients quantitatively and qualitatively during the manufacturing process.

⇨ Used to identify, quantify, purify the individual components of the mixture.

⇨ Used to water purification

⇨ Detection of impurities 

⇨ Used to check the purity and consistency of the products.

⇨ Used to evaluate formulation

Advantage of HPLC:

⇨ Enhance separation during shorter period of time.

⇨ Separation becomes faster.

⇨ Very small amount of solvent can be detected.

⇨ Sensitive selective detector

⇨ Get better resolution of compound from the column.

⇨ Improve resolution of the separation of the separated compound is achieved.

⇨ Separate, identify and quantify purify the sample

* Materials used in Stationary phase of RP-HPLC (Hydrophobic/Lipophobic/Non-polar in nature):

Hydrophobic materials such as-

⇨ Octadecyl Carbon Chain silica (C-18)

⇨ Cyano-bonded Silica

* Solvents used in Mobile phase of RP-HPLC (Hydrophilic/Polar in nature):

⇨Methanol

⇨ Water

Application of Reverse Phase HPLC:

⇨ hydrophilic/Lypophilic/Polar compounds are separared

* Materials used in Stationary phase of NP-HPLC (Hydrophilic/ Polar in nature):

⇨ Silica gel

* Solvents used in Mobile phase of NP-HPLC (Hydrophobic /Non-polar in nature):

⇨ Hexane

⇨ Carbon Tetracloride

Application of Normal Phase HPLC:

⇨ Hydrophobic/Lipophobic/Non-polar compounds are separated

Column Chromatography

Column chromatography is a technique which is used to separate a single chemical compound from a mixture dissovled in a fluid.

Column chromatography separates substances based on differential adsoption of compounds to the adsorbent as the compounds move through the column at different rates which allows them to get separated in fractions.

Application of Column Chromatography:

⇨ Isolating active ingredients

⇨ Separating compound mixture

⇨ Determining drug estimation from drug formulations

Gas Chromatography

Used for separating and analysing compounds that can be vaporized without decomposition. During operation, vaporized samples passes through column. Main purpose of Gass Chromatography is to separate the compounds that possesses-

⇨ High Volatility

⇨ Low molecular weight

⇨ Thermal Stability

Principle of Gass Chromatography:

Firstly, the process of separating the compounds in a mixture is carried out between a liquid stationary phase and a gas mobile phase, whereas in column chromatography the stationary phase is a solid and the mobile phase is a liquid. Hence the full name of the procedure is "Gas-Liquid Chromatography.

Secondly, the column through which the gas phase passes is located in an oven where the temperature of the gas can be controlled, whereas column chromatography has no such temperature control.

Thirdly, the concentration of a compound in the gas phase is solely a function of the vapor pressure of the gas.

Materials used in Stationary phase of Gas Chromatography:

Microscopic layer of viscous liquids such as-

⇨ Cyanopropylphenyl dimethyl polysiloxane

⇨ Biscyanopropyl cyanopropylphenyl polysiloxane

⇨ Diphenyl dimethyl polysiloxane

⇨ Carbowax polyethylene glycol

Solvents used in Mobile phase of Gas Chromatography:

Inert gases such as-

⇨ Helium gas

⇨ Argon gas

⇨ Nitrogen gas

⇨ Hydrogen gas

Detectors used in Gas Chromatography:

⇨ Flame ionization detector

⇨ Flame photometric detector

⇨ Thermal conductivity detector

⇨ Vacuum ultraviolet detector

⇨ Infrared detector

Application of Gas Chromatography:

⇨ Components being analyzed must be volatile, thermally stable and having molecular weight below 1250 Da.

⇨ Separate and measure organic molecules.

⇨ Help to produce pure products in large quanyities, ensure the purity of produced material.

⇨ Testing the purity of a particular substance

⇨ Food analysis: Ensuring the safety of food products

⇨ Measuring air pollution

⇨ Blood alcohol analysis

Gas chronatography vs Fractional distillation

Gas chromatagraphy is similar to fractional distillation, since both processes separate the components of a mixture primarily based on boiling point or vapour pressure differences.

Fractional distillation is typically used to separate components of a mixture on a large scale Whereas Gas chromatography can be used to separate a mixture on a much smaller scsample.

Ion exchange Chromatography

Materials used in Stationary phase of Ion exchange Chromatography:

Several matrix Materials such as-

⇨ Cellulose

⇨ Silica

⇨ Coated silica

⇨ Poly acryl amide

⇨ Acrylate co-polymer

Solvents used in Mobile phase of Ion exchange Chromatography:

⇨ EDTA

⇨ Polyols

⇨ Glycerol

⇨ Glucose

⇨ Saccharose

Application of Ion exchange Chromatography:

⇨ Used to separate charged biological molecules such as proteins, peptides, amino acids, nucleotides etc.

⇨ Used in treatment of water (Hard water)

⇨ Separation of Complex mixtures of biochemical compounds.

Paper Chromatography

⇨ It uses a strip paper as the stationary phase.

⇨ Capillary action is used to pull the solvents up through the paper and separate the solutes.

⇨ Solvent used in paper chromatography is moves through the paper due to capillary action.

Size exclusion chromatography

Materials used in Stationary phase of Size Exclusion Chromatography:

Various types of gels such as-

⇨ Polyacrylamide

⇨ Dextran

⇨ Agarose

⇨ Modified Polystyrene

Disintegration

Disintegration is the process by which a solid oral dosage form breaks up in water when measured in a standard apparatus. 

The usual disintegration time for uncoated tablets is 15 minutes, for film coated and hard gelatin capsules is 30 minutess and for Enteric coated & Sugar coated tablets is 60 minutes.

Disintegration time for various tablets according to USP-NF:

* For Uncoated tablet ⇨ 15 minutes

* For Film coated & Hard gelatin capsules ⇨ 30 minutes

* For Enteric & Sugar coated tablets ⇨ 60 minutes

Disintegration test requirement:

Number of Glass tube ⇨ 6 pices

Glass tube length ⇨ 3" long

Mesh size ⇨ 10 mesh screen

Temperature ⇨ 37 +/- 2°C

Rotation ⇨ 28 to 32 cycles per minute

N.B:

Particle size after disintegration ⇨ less than 2 mm diameter

Particle size after deaggregation ⇨ less than 0.25 mm diameter

Dissolution occur when particle size range become ⇨ less than 0.25 mm diameter

Dissolution

Dissolution is the process by which a solid drug substance becomes dissolved in a solvent.

Dissolution test stages with acceptable range

Stages// number of tablets

Stage 1 // 6 tablets ⇨ Not less than 5%

Stage 2// 12 tablets ⇨ 15% (but not more than 2 tablets)

Stage 3// 24 tablets ⇨ 5%

Stage 1 // 6 tablets ⇨ dissolved amount of each unit should not less than D+15%

Stage 2// 12 tablets ⇨ Average 12 units is eual to or greater than D and no unit is less than D-15%

Stage 3// 24 tablets ⇨ Average of 24 units is equal to or greater than D, not more than 2 units are less than D-15% and no unit is less than D-25%

[D= Dissolved active ingredient specified in the  individual monograph)

Classification of dissolution apparatus (USP):

Apparatus 1: Rotating Basket

Apparatus 2: Paddle Assembly (most widely used)

Apparatus 3: Reciprocating cylinder

Apparatus 4: Flow through cell.

Apparatus 5: Paddle over disk

Apparatus 6: Cylinder

Apparatus 7: Reciprocating holder

Friability

Friability is the ability of a solid substance to be reduced to smaller pieces with little effort.

The main purpose is to evaluate the ability of the tablets to withstand the breakage during the transportation and handling.

Friability limit

According to BP, percentage of friability should not be more than 0.8 % and according to USP should not be more than 1%.

Purpose of Friability test:

To evaluate the ability of the tablets to withstand the breakage during the transportation and handling.

Hardness

Hardness is also called crushing strength. It is the load required to crush the tablet when placed on its edge. Official standard for hardness of common tablet is 5-8 kg/cm2 and for sustained release tablets is 8-12 kg/cm2

Hardness tester

A device to test the hardness of tablet. 

By this tester the diameter, thickness and hardness are tested. 

The first reading for diameter, second reading for thickness and the third reading for hardness.

Function of Hardness tester:

First reading test indicate Thickness of tablet

Second reading test indicate Diameter of tablet

Third reading test indicate Hardness of tablet

Purpose of Hardness test:

Provide a meaningfull information about the amount of force required to fracture the solid dose tablet.

HLB Value

⇨ Hydrophilic-Lipophilic Balance

⇨ HLB value assigned to emulsifier

⇨It is useful in selecting the emulsifier or emulsifier blends for a formulation.

⇨ Generally larger the number is more water-soluble emulsifer

⇨ The HLB of a surfactant is a measure of the degree to which it is hydrophilic or lipophilic.

⇨ It is mainly applicable for non-ionic surfactant.

HLB Value (Hydrophilic Lipophilic Balance)

HLB range/ Surfactant application

0 - 3 ⇨ Antifoaming agents

4 - 6 ⇨ w/O emulsifying agents

7 - 9 ⇨ Wetting agents

8 - 18 ⇨ O/W emulsifying agents

13 - 15 ⇨ Detergents

10 - 18 ⇨ Solubilizing agents

Leak test

⇨ Check the leakage of the blister strip, sachets, bottle container etc.

⇨ This is a vacuum pump.

⇨ The test is done by colorful water.

Purpose of leak test:

⇨ Check the leakage of the blister trip, bottle container, sachets (containing tablets, granulates, liquids and so on)

⇨ Used to test the quality of packaging process 

⇨ Used to check that the seals enclosing the product are perfectly intact.

Loss on Drying

The expression of moisture content on a wet-weigth basis.

Claculation of Loss on Drying

LOD = (Weight of water in a sample/ total weight of wet sample)×100 = [Weight loss after test/ initial weight)× 100 = [(Initial weight - weight after test)/Initial weight]×100

Moisture Content

Measurement of the moisture in a wet solid on a dry weight basis.

Calculation of moisture content

MC = (Weight of water in a sample/ Weight of dry sample)×100 = [Weight loss after test/ Weight after test)× 100 = [(Initial weight - weight after test)/Weight after test]×100

LOD vs MC

⇨ The expression of moisture content on a wet-weigth basis

⇨ Measurement of the moisture in a wet solid on a dry weight basis.

LOD = (Weight of water in a sample/ total weight of wet sample)×100 = [Weight loss after test/ initial weight)× 100 = [(Initial weight - weight after test)/Initial weight]×100

MC = (Weight of water in a sample/ Weight of dry sample)×100 = [Weight loss after test/ Weight after test)× 100 = [(Initial weight - weight after test)/Weight after test]×100

LOD values can vary in any solid-fluid mixture from slightly above 0% to slightly 100%.

MC values can change from slightly above 0% and approach.

Moisture Analyzer

The moisture of the powder is test by this meter.

In a moisture analyzer machine contains a heater, a balance hare, a meter and a timer hare.

Solubility

⇨ Solubility is the indicative of maximum concentration that can be dissolved in the solvent to form a saturated solution.

Factors affecting solubility:

⇨ Forces between particles

⇨ Temperature

⇨ Pressure

Solubility range according to BP:

i) Very soluble substance ⇨ Parts of solvent required to dissolve 1 part of solute is : Less than 1

ii) Freely soluble substance ⇨ Parts of solvent required to dissolve 1 part of solute is : From 1 to 10

iii) Soluble substance ⇨ Parts of solvent required to dissolve 1 part of solute is : From 10 to 30

iv) Sparingly soluble substance ⇨ Parts of solvent required to dissolve 1 part of solute is : From 30 to 100

v) Slightly soluble substance ⇨ Parts of solvent required to dissolve 1 part of solute is : From 100 to 1000

vi) Very slightly soluble substance ⇨ Parts of solvent required to dissolve 1 part of solute is : 1000 to 10,000

vii) Partially insoluble substance ⇨ Parts of solvent required to dissolve 1 part of solute is : More than 10,000

Titration

Titration is the quantitative chemical analysis

Titration technique is used to determine the concentration of an identified analyte.

Indicator

Indicator is the weak acid or weak base which indicates the acid–base reaction by changing their in a ionized and unionized form. It also indicates the end point of a reaction.

Acid-Base Indicators

Indicator/ Colour in acidic condition/ Colour in basic condition/ pH range

Methyl orange/ Red/ Yellow/ 3.1— 4. 4

Methyl red/ Red/Yellow/ 4.4 — 6.3

Litmus/ Red/ Blue/ 5 — 8

Bromothymol blue/ Yellow/ blue/ 6 — 7.6

Phenolphthalein/ Colourless/ Pink/ 8.3 — 10

Types of titration

⇨ Acid-base titration

⇨ Redox titration

⇨ Gas phase titration

⇨ Complexometric titration

⇨ Zeta potential titration

⇨ Assay titration

⇨ Karl Fisher titration

⇨ Precipitation titration

⇨ Potentiometric titration

⇨ Conductimetric titration

⇨ Amperometric titration

⇨ Spectrophotometric titration

⇨ Iodometric Titration

⇨ Iodimetric Titration

Assay

Asay is a type of biological titration used to determine the concentration of virus or bacteria.

Complexometric titration

⇨ Volumetric analysis

⇨ Complexometric titration are usefull for determination of a mixture of different metal ion in solution.

⇨ Complexometric titration is done with EDTA which is act as Lewis base

⇨ Indicators used in Complexometric titration are various organic dyes such as–

1. Fast sulphon Black

2. Eriochrome Black T (Blue to Pink)

⇨ Eriochrome Red B

3. Murexide

In Complexometric titration metals to identified are form complex with EDTA (Metal cation -EDTA complex form)

⇨ In EDTA coloured complex is used to determine the end point of titration.

Types of Complexometric titration

1. Direct titration

2. Indirect titration

3. Back titration

4. Replacement titration]

*Application of Complexometric titration

⇨ The hardness of water can be estimated

⇨ Determine metal content in medicines

⇨ Numerous cosmetic product containing Titanium dioxide can be determine

⇨ Analysis of urine samples.

Back titration

In Back titration, the concentration of an analysis is determined by reacting it with a known amount of excess reagent.

The remaining excess reagent is then titrated with another second reagent.

Second titration result shows how much of the excess reagent was used in the first titration.

When Back titration is used?

⇨ When the acid or base is a insoluble salt. (ex. Calcium chloride)

⇨ When direct titration endpoint would be hard to discern ( Weak avid and weak base titration)

⇨ When reation occurs very slowly.

Redox Titration

Redox titration is based on oxidation-reduction reaction between the titrant and the analyte. Redox titration invovle a transfer of electrons between the given analyte and the titrant. Example of Redox titration:

⇨ Treatment of Iodine solution with reducing agent.

⇨ Titration of Potassium permanganate against oxalic acid

Types of Redox Titration:

⇨ Iodometry (Iodine)

⇨ Iodimetry (Iodine)

⇨ Bromatometry (Bromine)

⇨ Cerimetry (Cerium salts)

⇨ Permangatometry (Potassium permanganate)

⇨ Dichrometry (Potassium dichromate)

Iodometric Titration

Iodometric titration is an indirect titration method in which the amount of iodine is determined using oxidising agent. In iodometry, the iodine is oxidized first and subsequently reduced by the reducing agent.

Iodometric titration is a two step titration process.

Iodimetric Titration

Iodimetric titration is an direct titration method in which the amount of iodine is determined using reducing agent. In iodimetry, iodine is instantaneously reduced.

Iodimetric titration is a one step titration process.

Gas-Phase Titration

In gas phase titration, reactrants are present in the gas phase. The most common gas phase titration is based on beer Lambert law.

Gas-phase titration work by measuring the absorbance of light by the solution.

N.B: Beer-lambert law states that the absorbance of light is proportionate to the concentration of the solution.

Various types of gas-phase titration:

⇨ Ion-exchange gas phase titration

⇨ Redox gas phase titration

⇨ Fluorescence gas phase titration

⇨ UV-visible gas phase titration

⇨ Infrared gas phase titration

Example of gas-phase titration:

⇨ Titration of Carbon dioxide in the air.

⇨ Titration of Nitrogen in the air.

⇨ Titration of Oxygen in the air.

⇨ Titration of Chlorine in the air.

⇨ Titration of Bromine in the air.

⇨ Titration of Iodine in the air.

Karl Fisher Titration

A karl fisher titration determines the water content in a sample based on an iodine/iodide redox reaction. It is a titration method where water reacts with water until the water is consumed and the endpoint is reached. Karl fisher titration is advantageous over MC and LOD because KF is not affected by volatile compounds.

Functions of Karl Fischer Titration

⇨ Water determination using pyridine, sulfur dioxide and iodine.

Total Organic Carbon (TOC)

Total organic carbon is the amount of carbon bound in an organic compound and is often used as a non-specific indicator of water quality or cleanliness of pharmaceutical manufacturing equipment.

Functions of TOC:

⇨ Used as non-specific water quality

⇨ Measure both total carbon present (so called inorganic carbon),  dissolved carbon dioxide and carbonic acid salts.

Temperature 

Temperature conversion rule:

C/5 = (K-273.15)/5 = (F- 32)/9

Temperature Condition according to BP:

For Deepfreeze ⇨ below —15°C

For Refrigerator ⇨ 2—8° C

For Cold/Cool ⇨ 8—15° C

For Room temperature ⇨ 15—25° C

Weight variation of Tablets

Weight variation of Tablets:

Average weight ⇨ Maximum % Variation allowed

(According to BP)

</= 80 mg ⇨ maximum 10% variable allowed

80-150 mg ⇨ maximum 7.5% variation allowed

>150 mg ⇨ maximum 5% variation allowed

(According to USP)

<= 130 mg ⇨ maximum 10% variation allowed

130-324 mg ⇨ maximum 7.5% variation allowed

>324 mg ⇨ maximum 5% variation allowed