Pharmaceutical Quality Control

Quality

Acoording to British Standard Institute' Definition: 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 Product

Quality product is that product which have therapeutic efficacy and safe for patient. It cures or prevents diseases but does no harm to patient.

Attributes of Quality Medicine

Efficacy, Safety, Stability,  Potency, Purity, Regulatory Compliance.

Quality control

Quality control covers all measurements taken including the setting of specifications, sampling, testing and analytical clearance, to ensure that raw materials, intermediates, packaging materials and finished pharmaceutical products conform with established specifications for identity, stregth, purity and other characteristics.

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

Quality control= Testing + Assessment

Basic requirements of Quality Control

☞ The finished products containers must comply with specification.

☞ Approved procedures

☞ Trained personnel

☞ Correct sampling methods

☞ Validation testing methods

☞ Sufficient retained samples of starting materials, packaging materials and finished products.

☞ All batches are reviewed and released by a qualified person to approved procedures.

☞ Records are kept of as sampling, inspecting and testing procedures

☞ Product label check

Key Responsibilities of Quality Control Department

☞ Sampling adequately for testing purpose (Physical, Chemical & Biological)

☞ Issuing release, reject or quarantine advice for each batch of raw and packaging materials.

☞ Assesment of intermediate products for further processing.

☞ Assessment of the bulk products for their release, reprocessed and reject etc.

☞ Storing keeping samples for each batch produced.

☞ Ensure precision and accuracy of all testing methods.

☞ Performing environmental monitoring checks calibration and standardization of laboratory equipment.

☞ Control of laboratory reagents.

☞ Testing of any return goods.

☞ Analysis of complaint samples with their corresponding receiving samples.

☞ Monitoring batch-wise full quality control test records with signature of the persons who performs the test.

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.

Packaging materials sampling plan

Finished Products sampling plan

How do you prepare a sample for Analysis?

What is the goal for Sampling Preparation?

Quality Control Instruments

⇨ HPLC

⇨ UPLC

⇨ GC/GC-MS

⇨ AAS

⇨ LC-MS/LC-MS-MS

⇨ TOC

⇨ SEC

⇨ IC

⇨ HPTLC

⇨ FTIR

⇨ Spectophotometer

⇨ UV-visible spectrophotometer

⇨ Raman Spectrophotometer

⇨ Autoclave

⇨ Fume hood

⇨ Particle size Analyzer

⇨ Incubator

⇨ Melting point apparatus

⇨ Incubator

⇨ Dissolution Tester

⇨ Disintegration Tester

⇨ Hardness Tester

⇨ Friability Tester

⇨ pH Meter

⇨ Conductivity Meter

⇨ Centrifuge Machine

⇨ Microscope

⇨ Turbidity Meter

⇨ Balance

⇨ Colorimetric Titrator

⇨ Electronic Heating Mantle

⇨ Flame Photometer

⇨ Karl Fisher Titrator

⇨ Moisture Analyzer

⇨ Muffle Furnace

⇨ Orbital Shaker

⇨ Osmometer

⇨ Pack Integrity Tester

⇨ Polarimeter

⇨ Potentiometer/Potentiometric Titrator

⇨ Refractometer

⇨ Rotary Evaporator

⇨ Shieve Shaker

⇨ Tap Density Tester

⇨ TLC

⇨ Viscometer

Quality Control vs Quality Assurance

Quality Control	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.

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)

Mobile Phase

The mobile phase in chromatography is the phase that is either liquid or gas that is passed through a chromatographic system where the components of the mixture are separated at different rates by adsorbing them to the stationary phase.

Stationary phase

The stationary phase in chromatography is the phase that is either a solid or liquid particle attached to a glass or a metal surface on which the components of the mixture to be separated is absorbed selectively.

Differences between Mobile phase and Stationary Phase

Features	Mobile Phase	Stationary Phase
Definition	The mobile phase in chromatography is the phase that is either liquid or gas that is passed through a chromatographic system where the components of the mixture are separated at different rates by adsorbing them to the stationary phase.	The stationary phase in chromatography is the phase that is either a solid or liquid particle attached to a glass or a metal surface on which the components of Calibra to be separated is absorbed selectively.
Movement	Thr moblie phase is migrates through the stationary phase.	The stationary phase does not move.
Phase of matter	The mobile is either a gas or liquid.	The stationary phase is,either a solid compound or a liquid, supported on a solid.
Sample Dissolution	The Mobile phae is completely dissolves the sample.	The stationary phase may or may not have interactions with the componemts in the sample.

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.

History of HPLC

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.

Main Parts of a HPLC

☞ Solvent Reservoir

☞ Pump

☞ Injector

☞ Column

☞ Detector

☞ Data System

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 are used.

⇨ 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

Retention Time (RT)

The retention time is the amount of time it takes for the compound to pass through the column.

Relative Retention Time (RRT)

The relative retention time is the comparision of the Retention time of one compound to another.

Tailing Factor

The tailing factor is a measure of peak tailing. It is defined as the distance from the front slope of the peak to the back slope divided by twice the distance from the center line of the peak to the front slope, with all measurements made at 5% of the maximum peak height.

* 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.

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.

Rf Value

The ratio of distacolumne compound travels to the distance the solvent front travels is called Rf Value.

Rf value is calculated using the following formula:

Rf =Distance traveled by substance/Distance traveled by solvent

Liquid Chromatography

Liquid chromatography is a separation technique where the mobile phase used is liquid, and the separation can take place either in a column or a plain surface.

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.

Principle of Liquid Chromatography

☞ The process of liquid chromatography is based on the principle for the affinity of the molecules to the mobile phase.

☞ If the components to be separated have a higher affinity to the mobile phase,  the molecules move along with the mobile phase and come out of the column faster.

☞ However, if the components have a lower degree of interaction with the mobile phase, the molecules move slowly and thus come out of the column later.

☞ Thus, if two molecules in a mixture have different polarities and the mobile phase is of a distinct polarity, the two molecules will have at different speeds through the stationary phase.

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 adsorption 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

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

⇨ High Volatility

⇨ Low molecular weight

⇨ Thermal Stability

Principle of Gas 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.

Gss chromatography is also similar to fractional distillation, since both processes separate the components of a mixture primarily based on boiling point (or vapor pressure) differences. However, fractional distillation is typically used to separate the components of a mixture on a large scale, whereas GC can be used on a much smaller scale (microscale).

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.

Types of Coumn used in GC:

There are two general types of columns are used in GC.

☞ Packed GC column

☞ Capillary GC column also known as open tubular.

Which gases are used in GC?

☞ Helium gas

☞ Nitrogen gas

☞ Hydrogen 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 quantities, ensure the purity of produced material.

⇨ Testing the purity of a particular substances

⇨ Food analysis: Ensuring the safety of food products

⇨ Measuring air pollution

⇨ Blood alcohol analysis

Liquid Chromatography-Mass Spectroscopy

LC-MS is an analytical chemistry technique that comvines the physical separation capabilities of liquid chromatography with the mass analysis capabilities of mass spectroscopy. The combined technique between MS and HPLC is commonly known as LC-MS.

Principle of LC-MS

The LC-MS technology involves use of an HPLC, wherein the individual components in a mixture are first separated followed by ionization and separation of the ions on the basis of their mass/charge ratio. The separated ions are then directed to a photo or electron multiplier  tube detector, which identifies and quantifies each ion. The ion source is an important component in any MS analysis, as this basically aids in efficient generation of ions for analysis.

Size Exclusion Chromatography

SEC is also known as molecular sieve chromatography, is a chromatographuc method in which molecules in solutions are separated by their size and in some cases molecular weight.

Principle of SEC

The selection of molecules on the basis of their molecular size and shape utilizes the molecular sieve properties of a variety of porous materials. Probably the most commonly used of such materials are a group of polymeric organic conpounds which possess a three-dimensional network of pores which confer gel properties upon them. The general principle of exclusion chronatography is quite simple. A column of gel particles or porous glass granules is in equilibrium with a suitable solvent for the molecules to be separated. Large molecules which are completely excluded from the pores will pass through the interstitial spaces, while smaller molecules will be distributed between the solvent inside and outside the molecular sieve and will then pass through the column at a lower rate.

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

Paper chromatography is one of the most common types of chromatography. It uses a strip of paper as the stationary phase. Capillary action is used to pull the solvents up through the paper and sepsrate the solutes. Paper chromatography is a procedure used to separate substances in a mixture.

⇨ 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.

Basic Principles of Paper Chromatography

A small concentrated sample of a mixture is placed on the chromatography paper above the line of a solvent mixture. The paper is contact with a solvent solution at its bottom. This solvent moves through the paper due to capillary action and dissoles the mixture spot. Sone parts of the solvent mixture to be separated have a greater attraction for the chromatography paper, so they move a lesser distance, while other parts of the solvent mixture have a lesser attraction, so they move a greater distance up the paper.

Size exclusion chromatography

Materials used in Stationary phase of Size Exclusion Chromatography:

Various types of gels such as-

⇨ Polyacrylamide

⇨ Dextran

⇨ Agarose

⇨ Modified Polystyrene

Spectroscopy

⇨ Atomic Absorption Spectroscopy

⇨ IR spectroscopy

⇨ Fourier transform Infra-red Spectroscopy

⇨ Nuclear Magnetic Spectroscopy

⇨ UV-visible spectroscopy

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.

Infrared (IR) Spectroscopy

Infrared spectroscopy is the spectroscopy that deals with Infrared region of the electromagnetic spectrum, that is light with a longer 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.

Roman Spectroscopy

Roman spectroscopy is an analytical technique where scattered light is used to measure the vibrational energy modes of a sample. Raman spectroscopy is commonly used in chemistry to provide a structural fingerprint by which molecules can be identified.

Principle of Raman Spectroscopy

When light interact with molecules in a gas, liquid or solid, the vast majority of the photons are dispersed or scattered at the same energy as the incident photons. This is described as elastic scattering or Rayleigh scattering. A small number of these photons,  approximately 1 photon to 10 million will scatter at a different frequency than the incident photon. This process is called inelastic scattering or the Raman effect. Raman allows the user to collect the vibrational signature of a molecule,  giving insight into how it is put together, as well as it interacts ith other molecules around it.

Nuclear Magnetic Resonance

NMR is a physical phenomenon in which nuclei in a magnetic field absorb and re-emit electromagnetic radiation. This energy is at a specific resonance frequency which depends on the strength of the magnetic field and the magnetic properties of the isotope of the atoms.

Principle of NMR

The principle of NMR is usually involves two sequential steps:

☞ The alignment (Polarization) of the magnetic nuclear spins in an applied, constant magnetic field Ho.

☞ The perturbation of this alignment of the molecular spins by employing an electro-magnetic, usually radio frequency pulse. The required perturbing frequency is dependent upon the static magnetic field (Ho) and the nuclei of observation.

The two fields are usually chosen to be perpendicular to each other as this maximizes the NMR signal strength. The resulting response by the total magnetization of the nuclear spins is the phenomenon that is exploited in NMR spectroscopy and magnetuc resonance imaging. Both use intense applied magnetic field in order to achieve dispersion and very high stanility to deliver spectral resolution, the details of which are described by chemical shifts, the Zeeman effect, and Knight shifts (in metals). NMR phenomenon are also utilized in low-field NMR. NMR spectroscopy and MRI in the Earth's magnetic field and in several types of magnetometers.

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

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.

Basic Principle of AAS

The technique makes use of absorption spectrometry to assess the concentration of an analyte in a sample. It requires standards with known analyte content to establish the relation between the measured absorbance and the analyte concentration and relies therefore on the Beer-Lambert Law.

In short, the electrons of the atoms in tge atomizer can be promoted to higher orbitals (exvited state) for a shor period of time (nanoseconds) by absorbing a defined quantity of energy (radiation of a given wavelength).  This amount of energy, i.e. wavength is specific to a particular electron transition in a particular element. In general, each wavelength corresponds to only one element and the width of an absorption line is only of the order of a few picnometers, which gives a sample and eith a sample in the atomizer is measured using a detector, and the ratio between the two values (the absorbance) is converted to analyte concentration or mass using the Beer-Lambert Law.

Functions of AAS

⇨ Quantitative determination chemical elements

⇨ Metal Identification

Advantages of AAS

☞ Wide spread application

☞ High sensitivity

☞ Freedom from interference

☞ Simplicity in Operation

☞ Moderate cost

Disadvantages of AAS

☞ Does not determine non-metals.

☞ Determines only one element in one time.

☞ Destructive method of analysis.

Total Organic Carbon (TOC)

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

TOC is also refer to the amount of organic carbon in a geological formation, particulsrly the source rock for a petroleum play; 2% is a rough minimum. For marine surface sediments, average TOC content is 0.5 wt% in the deep ocean and 2 wt% along the eastern margins.

A typical analysis for TOC measures both the total carbon present and the so-called "inorganic carbon", the latter representing the content of dissolved carbon dioxide and carbonic acid salts. Substracting the inorganic carbon from the total carbon yields TOC. Another common variant of TOC analysis involves removing the IC portion first and then measuring the leftover carbon. This method involves purging an acidified sample with carbon-free air or nitrogen prior to measurement and so is more accurately called non-purgeable organic carbon (NPOC).

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

Karl Fisher Titration

Karl Fisher: Kart Fisher was the scientist who in 1935 developed the original Karl Fisher method for water determination using Pyridine, Sulfur dioxide and Iodine.

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.

Step-1: SO2 + MeOH + B ⇨ MeSO3 +HB+

Step-2: MeSO3- +H20 + I2 + 2B ⇨ MeSO4 + 2HB- + 2I-

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.

pH & pH meter

pH: pH is the negative logarithm of hydrogen ion concentration.

pH meter

A pH meter is an electronic device used for measuring the pH of a liquid. A typical pH meter consists of a special measuring probe connected to an electronic meter that measures and displays the pH reading.

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.

Viscometer

A viscometer is an instrument used to measure the viscosity of a fluid. Viscometer can only be used on fluids that have a stable viscosity, despite how they are flowing. To properly measure a fluid, either the fluid or the viscometer hss to remain stationary.

Name of different viscometer:

☞ U-tube (Ostwald) Viscometer

☞ Falling sphere viscometer

☞ Falling Ball Viscometer

☞ Falling Piston zviscometer

☞ Oscillating Pisyon Viscometer

☞ Vibrational Viscometer

☞ Rotational Viscometer

☞ Electromagnetically Spinning Sphere Viscometer (EMS Viscometer)

☞ Stabinger Viscometer

☞ Bubble Viscometer

☞ Rectangular-Slit Viscometer

Osmometer

An osmometer is a device for measuring the osmotic strength of a solution, colloid or compound. There are three major types of osmometer commercially available, each leveraging a particular colligative property to achieve their analytical results.

Refractometer

A refractometer is a laboratory or field device for the measurement of an index of refraction (refractometry).

Types of Refractometer

There are four main types of refractometer:

1. Traditional handheld refractometer: A traditional handheld refractometer is an analog instrument for measuring a liquid's refractive index.

2. Digital Handheld Refractometer: A digital handheld refractometer is an instrument for measuring the refractive index of materials.

3. Abbe Refractometer: An Abbe refractometer is a bench-top device for the high-precision measurement of an index of refraction.

4. Inline Process Refractometer: Inline process refractometers are a type of refractometer designed for the conyinuous measurement of a liquid flowing through a pipe or inside a tank. These refractometers typically consist of a sensor, placed in line with the fluid flow, coupled to a control box.

Incubator

In biology, an incubator is a device used to grow and maintain microbiological cultures or cell cultures. The incubator maintains optimal temperature, humidity, and other conditions such as the carbon dioxide and oxygen content of the atmosphere inside.

Incubators are essential for a lot of experimental work in cell biology, microbiology and molecular biology and are used to culture both bacterial as well as eukaryotic cells.

Centrifuge

A centrifuge is a piece of equipment,  generally driven by an electric motor that puts an object in rotation around a fixed axis,  applying a potentially strong force perpendicular to the axis.

Centrifugation

Centrifugation is a process which involves the use of the centrifugal force for the sedimentation of heterogeneous mixtures with a centrifuge, used in industry and in laboratory settings. This process is used to separate two immiscible liquids. More-dense components of the mixture migrate away from the axis of the centrifuge, while less-dense components of the mixture migrate towards the axis.

Polarimeter

A polarimeter is a scientific instrument used to measure the angle of rotation caused by passing polarized light through an optically active substance.

Polarimetry

Polarimetry is the measurement and interpretation of the polarization of transverse waves, most notably electromagnetic waves, such as radio or light waves. Typically polarimetry is done on electromagnetic waves that have traveled through or have been reflected, refracted or diffracted by some material in order to characterize that object.

Optical Rotation

Optical Rotation is the turning of the plane of linearily polarized light about the direction of motion as the light travels through certain materials. It occurs in solutions of chiral molecules such as sucrose,  solids with rotated crystal planes such as quartz and spin-polarized gases of atoms or molecules.

Muffle Furnace

A muffle furnace is a furnace in which the subject mateial is isolated from the fuel and all of the products of combustion, including gases and flying ash. It is furnace or a device in which the samples can be tested at high temperature. The walls of the device heat the content which is placed inside the temperature radiantly so that the material does not cone in direct contact with flame. Muffle furnace is widely used to test laboratories with a compact means to create a high temperature say up to 1200 degree celcius to tesr the charactetistics of the material for highly accurate test results.

Hardness

Hardness is also so-called crushing strength. It is the load required to crush the tablet when placed on its edge. Tablet requires a certain amount of strength or hardness and resistance to friability to  withstand mechanical shakes pf handling in manufacture, packaging and shipping.

Official standard for hardness of common tablet is 5-8 kg/cm2 and for sustained release tablets is 8-12 kg/cm2

Hardness tester

Hardness tester is 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.

Units of measurement of Tablet hardness:

☞ Kilogram (Kg)

☞ Newton (N)

☞ Pound (Ib)

☞ Kilopound (Kp)

☞ Strong-Cobb (SC)

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 ⇨ NMT 15 minutes

* For Film coated & Hard gelatin capsules ⇨ NTM 30 minutes

* For Enteric & Sugar coated tablets ⇨ NMT 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.

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.

Calculation 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

Loss on Drying	Moisture Content
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.

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

Titration

Titration is the quantitative chemical analysis

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

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.

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

Friability

Weight variation of tablet

Weight variation of capsule

Uniformity

Disintegration

DIssolution

Dissolution Apparatus

Dissolution apparatus classification

Dissolution test stage

Why is dissolution test required?

How dissolution test is performed?

Which tablets are used in calibration of dissolution apparatus?

Non-disintegrating tablets: Salicylic acid

Disintegrating tablets,: Prednisolone tablets

Disintegration vs dissolution

Disintegration	Dissolution
Breakdow substances into tiny granules, molecules or particles.	Dissolve substance in different solvents.
Apllied on solid substances.	Apllied on liquid, gaseous and solid substances.
Can precede dissolution in breaking substance of low solubility.	Happens after substances with low solubility are broken down. But can happen in the absence of disintegration.

Moisture content

Loss of drying

MC vs LOD

Bulk density

Characteristic of powder rather than of individual particles given by the mass of powder occupying a known volume.

Bulk density is a property of powders, granules and other "divided" solids, especially used in reference to mineral components, chemical substances,  ingradients, foodstuff or any other masses of corpuscular or particulate matter. It is dwfined as the mass of many particles of material divided by the total volume they occupy. The total volume includes particle volume, inter-paryicle void volume and internal pore volume. Bulk density is not an intrinsic property of a material; it is depending on how the material is handled.

Bulk density = Mass of soil/Volume as a whole.

Tapped density

It is term used to describe the bulk density of a powder after consolidation/compression prescribed in terms of 'tapping' the cantainer of powder a measured number of times, usually from a predetermined height.

Leak testing

Check the leakage of the blister strip, sachets bottle container etc. There is a vacuum pump. The test is done by colorful water.

Leak test apparatus

It is used to test for the integrity of packed strips, blisters and small sachets containing tablets,  granulates, liquids and so on. The instrument is used to test the quality of the packaging process and to check that the seals enclosing the product are perfectly intact.

Indicator used in leak test apparatus

In order to identify the leakage in blister strip or sachets or bottle container Methylene blue color is used in the leak test apparatus.

Melting point

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.

Calibration instrument flow chart

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	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.
Calibration ensures instruments gives correct reading.	Validation ensures the entire method or process consistently produces the intended results.
Example: Adjusting a weighing balance to show correct weight.	Example: Confirming that a Tablet manufacturing process consistently produces tablets of correct quality.

Standard

The word standard means a material containing a substance of our interest with a known concentration.

Primary Standard

Primary standards is a reagent which is very pure, generally representatives of the number of moles the substance contains and easily weighed. A primary standard is a meadurement that is used in the calibration of working standards.

Working standards

Working standards is a standard that is routinely to calibrate or check material measures, measuring instruments or reference materials. A working standard is usually calibrated against a reference standard.

Secondary Standard

Secondary standard is a chemical that has been standardized against a primary standard for use in a specific analysis. Secondary standards are commonly used to calibrate analytical methods.

Impurity

Impurities in pharmaceuticals are the unwanted chemicals that even in small amounts may influence the efficacy and safety of the pharmaceutical products. An impurity is any component of the product which is not the chemical entity defines as the active substance or an excipient in the product.

Impurities commonly in chemical substances include small quantities of Lead, Arsenic, Iron, Chloride & Sulphate.

Classification of Impurities

a) Organic impurities: Such as Starting materials, By-products, Intermediates, Degradation products, Reagents, Ligand & Catalyst

b) Inorganic impurities: such as Reagents, Ligand & Catalyst, Heavy metals, Inorganic salts, Charcoal

c) Residual impurities

Syatem suitability

Syatem suitability is to prove that system is working perfectly before the analysis. It is used to verify the chromatographic system is suitable for the intended analysis. System suitability test is an essential part of HPLC & GC methods.

Parameters of System Suitability Testing

☞ Resolution

☞ Retention Time

☞ Pressure

☞ Column Efficiency

☞ Repeatability

☞ Plate Number

☞ Tailing factor

☞ Signal-to-noise Ration

Resolution

Resolution is one of the most important parameters. Resolution is used to check whether the critical separation is feasible under the given conditions.

Retention Time

Retention time is one of the easy-to-identify parameters. The resolution should be fairly constant. This is because values outside the retention-time window might go unreported by the system under test.

Pressure

The suitability testing must be carried out within set presure limits. This is to ensure that wearing of system is reduced. The column is efficiency-also known as broadening.

Repeatability

Successive measurements taken under the same measurement conditions should give the same results.

Theoretical plate number

The plate number is a theoretical plate index used to determine column efficiency.  The plate number is arrived at by using the plate theory. Plate number changes depending on the type of analysis carried out.

Tailing factor

This is called a Symmetry factor. Tailing factor becomes important if the peak tailing has chances of affecting the method's performance. Similar to Plate number, the tailing factor also depends upon the type of analysis.

Single-to-Noise Ratio

Single-to-Noise Ratio is a measure of the system's performance at the lower end.

Analyte

Analyte is the substance to be identifued, detected or separated in some manner.

Types of Analysis

There are two types of Analysis:

1. Qualitative Analysis

2. Quantitative Analysis

Qualitative Analysis

Qualitative analysis is performed to identify what material/analyte present in a sample.

☞ Qualitative analysis is concerned with the analysis of data that cannot be quantified. This type of data is about the understanding and insights into the properties and attributes of objects.

☞ Qualitative analysis can get a deeper understanding of "why" a certain phenomenon occurs.

Quantitative Analysis

☞ Quantitative analysis is an analysis to determine how much of a material is present in a sample.

☞ Quantitative analysis is often associated with numerical analysis where data is collected, classified and then computed for certain findings using a set of statistical methods. Data is chosen randomly in large samples and then analyzed.

Differences between Qualitative and Quantitative Analysis

Qualitative Analysis	Quantitative Analysis
It is a subjective analysis that is more concerned with non-statistical data that cannot be computed.	It is an objective analysis that quantifies data.
Typical data include color, gender, nationality, region and many more.	Typical data include measurable quantities such as length, size, weight, mass and many more.
The analysis is used to understand why a certain phenomenon occurs.	The analysis is concerned with how many or how much a certain phenonenon occurs.
Sample is small and is non-representative of the entire population.	The sample is large and can be generalized to cover the entire population.
Qualitative analysis interpret and undertand social interactions.	Quantitative analysis test hypotheses and give future prediction.
Research methodology is often exploratory.	Research methodology is often conclusive.

Titration

Indicator

Buffer Solution

A buffer solution is an aqueous solution consisting of a mixture of a weak acid and its conjugate base or vice versa. Its pH changes very little when a small amount of strong acid or base is added to it. Buffer solutions are used as a means of keeping pH at a nearly constant value in a wide variety of chemical applications.

Types of Buffer solution

Buffer solutions are of two types:

a) Acidic buffer: An acidic buffer solution is obtained by dissolving a weak acid & salt of weak acid with strong base in water.

b) Basic buffer: A basic buffer solution is obtained by dissolving a weak base & salt of weak base with strong acid in water.

Normality

Normality is the equivalent weight of solute dissolved in one litre of the solution.

Normality = Gram equivalent weight of solute/Lutre of solution

Normality = Number of equivalent of solute × Molariyy of Solution

Molarity

Molarity is the number of moles of solute dissolved in one liter of the solution.

Molality

It is the number of molecules of solute dissolved in 1000g (,1 kg) of solvent.

Mole fraction

It is the ratio of the number of moles of solute to the total number of moles of the solution.

Normal solution

A normal solution is a solution that contain 1 gram equivalent weight of solute per litre of solution. The gram equivalent weight is equal to the molecular weight expressed as grams divided by the valency of the solute.

Molar Solution

A 1 nolar solution is a solution in which 1 nole of a compound is dissolved in a total volume of 1 litre.

Solubility

Solubility is the indicative of maximum concentration that can be dissolved in the solvent to form a saturated solution. Thus it is expressed as grams of solute dissolving in volume of solvent.

Factors affecting solubility

☞ Forces between particles

☞ Temperature

☞Pressure

Solubility range according to BP

Relative Expression	Parts of solvent required to disslove 1 part of solute
Very soluble	Less than 1
Freely soluble	From 1 to 10
Soluble	From 10 to 30
Sparingly soluble	From 30 to 100
Slightly soluble	From 100 to 1000
Very slightly soluble	From 1000 to 10000
Practically insoluble	More than 10000

Temperature

Temperature conversion instructions

Temperature conditions according to BP&USP/NF

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

Raw materials testing parameters

☞ Description

☞ Appearance of solution

☞ Identification

☞ Crystallinity

☞ Bulk Density

☞ pH

☞ Residue on ignition

☞ Solubility

☞ Melting point

☞ Clarity

☞ Color

☞ Assay

☞ LOD/MC

☞ Dissolution

☞ Viscosity

☞ Chromatographic purity

☞ Organic Volatile impurities

☞ Refractive Index

☞ Specific Optical Rotation

Finished Product testing parameters of Tablets

☞ Appearance

☞ Individual weight

☞ Average weight

☞ Uniformity of weight

☞ Uniformity of content

☞ Hardness

☞ Thickness

☞ LOD

☞ Assay

☞ Length

☞ Friability

☞ Disintegration

☞ Dissolution

☞ Weight variation

☞ RSD

☞ Width

☞ Content of active ingredient

Finished Product testing parameters of Capsule

☞ Appearance

☞ Individual weight

☞ Average weight

☞ Uniformity of weight

☞ Uniformity of content

☞ Assay

☞ Disintegration

☞ Weight variation

☞ RSD

☞Moisture content by Karl Fisher

Finished Product testing parameters of Oral liquid

☞ Appearance

☞ pH

☞ Average weight

☞ Uniformity of weight

☞, Weight variation

☞ Viscosity

☞ RSD

☞ Sterility

☞ Identification of active ingredient

☞ Microbial limit

☞ Homogenicity

☞ Assay

Finished Product testing parameters of Aerosol & Spray

☞ Appearance

☞ Leak Test

☞ Particle size

☞ Pressure test

☞ Net content

☞ RSD

☞ Identification of Activie ingredient

Finished Product testing parameters of Injectable dosage form

☞ Appearance

☞ Leak Test

☞ pH

☞ Viscosity

☞ Net content

☞ Osmolarity

☞ Assay

☞ RSD

☞ Identification of Activie ingredient

☞ Pyrogen test

☞ Sterility test

☞ Volume check

☞ Clarity test

Blister foil testing parameters

☞ Description

☞ Text

☞ Colour

☞ Width

☞ Thickness

☞ Grammage

☞ Surface area

☞Mqchine Triali

Amber glass bottle testing parameters

☞ Description

☞ Dimensions

☞ Weight

☞ Capacity

☞ Light Transmission

Labels testing parameters

☞ Description

☞ Text

☞Colour

☞ Dimensions

☞Grammage

☞ Visual inspection for defects

PVC/PVDC testing parameters

☞ Description

☞ Text

☞ Colour

☞ Dimensions

☞ Width

☞ Machine trial

☞ Thickness

☞ Surface area

☞ Gramnage (g/m2)

Shipping carton testing parameters

☞ Description

☞ Text

☞ Colour

☞ Dimension

☞ Weight

☞ Adhesiveness to mask tape

☞ Adaptability

Drug Purity

Drug purity is the absence of unwanted substance like impurity & contamination.

Drug Potency

Drug potency is a measurement of amount of two drugs to produces same effect.

Specific Gravity

Specific gravity is the ratio of the density of a substance to the density of a referencce substance.

Viscosity

The viscosity of a fluid is a measure of its resistance to deformation at a given rate.

Unit of viscosity

The SI unit of the viscosity is Pascal-Second (Pa.S) & the CGS unit is the poise (P)

Relationship between Viscosity and Temperature

Solute

A solute is a substance that is added to a solvent to form a solution.

Solvent

A solvent is a substance that dissolves the solute particles during the formation of a solution.

Differences between Solute and Solvent

Features	Solute	Solvent
Definition	A solute is a substance that is added to a solvent to form a solution.	A solvent is a substance that dissolves the solute particles during the formation of a solution.
Phase	The solute is the dispered phase of a solution.	The solvent is the medium phase of a solution that disperse solute particles.
Quantity	The quantity of solute is less than the solvent in a solution.	The quantity of solvent is more than the solute in a solution.
Physical State	Solute might exist in a solid, liquid or gaseous state.	Most solvents are in a liquid state, but solvents might exist in the gaseous state.
Heat Transfer	In a solution, heat is transferred to the solute.	In a solution, heat is transferred from the solvent.
Boiling Point	The boiling point of the solute is higher than that of the solution.	The boiling point of solvents is lower than that of solutes.
Examples	Salt in Seawater, Protons in Cytosol, Sugar in tea etc	Water, Hydrocarbons, Alcohols, Esters etc.