Types of Instruments Used in Pharmaceutical Industry

In the pharmaceutical industry, manufacturers invest heavily in manufacturing machines and systems for the compliant production process to allow their finished products to compete with their competitors. Secondly, to enable their products to deliver the required results intended its user. Apart from processes and systems, it is also mandatory for the manufacturers to develop and maintain a system that keeps an eye on the product’s production process from the initial stages of raw material selection to final product packaging.

The pharmaceutical industry uses different instruments to maintain a check on the quality of each manufacturing cycle. They are used to inspect every single component of the product, each manufacturing process stage, and post-production product’s quality.

The equipment for pharmaceutical industry is also responsible for proper maintenance such as calibration, validation, and Troubleshooting to keep them in optimum working condition. In addition to this, proper storage and working environment are also necessary for their correct operation.

Every manufacturer is required by regulatory bodies to keep appropriate instruments following their guidelines. Regulator bodies keep a close eye on the manufacturer’s approach towards instrumentation during accreditation and inspection. It can also result in failed accreditation and license cancellation if regulatory find any deviation in compliance.

Areas of Applications

In a pharmaceutical manufacturing plant, instrumentation are commonly used in the following departments

Quality Control Department - QCD

The quality control department is one of the critical departments in a pharmaceutical manufacturing facility. It is used for product development and manufacturing product testing. Following are essential characteristics of instrumentation in a QCD.

· The person performing testing procedures (or analysts) should be an expert in handling and using the instruments. They should be well aware of the basic concept of each instrument and the purpose of each instrument in the pharmaceutical testing cycle.

· Instruments should be appropriately calibrated with regular frequency, with proper record keeping. Calibration record is an integral part of regulatory body inspection qualification. The calibration frequency can be set according to the instrument's usage or the manufacturer's recommendation.

· Every QC lab is responsible for maintaining the usage log. The log indicates the detailed activity of a particular instrument with time, personnel, and type of measurement made.

Quality Assurance Department – QAD

The quality assurance department is responsible for maintaining the product’s quality during the production process, from the initial stages of raw material issuance to final product packaging. Personnel from QAD are deployed on every manufacturing process, and they regularly test samples of products from the different production stages.

Sometimes they perform the test on the instruments installed at the production floor, such as in the in-process lab. Sometimes, QAD has a dedicated lab with all the necessary required instruments.

Production department – In Process labs

Pharmaceutical instruments are also installed on the production floor so that that production personnel can check production process parameters. A dedicated room or space is allocated for the instruments on the production floor, often called the In-Process lab.

The production personnel must measure and record the process parameters during the production process. These records become part of production documentation. In addition to production personnel, Quality Assurance and Control personnel also uses instruments in the In-Process lab.

Instruments used in Pharmaceutical Industry

Let’s look at some instruments commonly used in Pharmaceutical industry

Karl Fischer titrator

Karl Fischer titrator is an instrument used to perform titration on chemicals. Karl Fischer invented this technique, which is named after its inventor. It is used to detect or measure the amount of water concentration in a pharmaceutical product. Karl Fischer's titration differs from the common titration technique, as typical titration is used to detect the concentration of an unknown solution with a solution of known concentration. Whereas Karl Fischer's titration consumes water, it can only be used for water-related measurements.

Water is used as a solution of known concentration in buffer form. A double platinum electrode is used as an indicator that changes color, indicating the end of the reaction. The color change occurs due to an excess of iodine at the electrode. The color change occurs when the total amount of water concentration is consumed. The amount of reagent consumed in a reaction indicates the total water concentration in a given sample.

There are two types of Karl Fischer titration techniques – Volumetric and Coulometric. Their selection depends upon the amount of water concentration in the sample.

The titrant is added physically through laboratory instruments such as burette in the Volumetric method. This method is suitable for samples having more significant quantities of water, such as in the range of 0.1 mg to 500mg. 

There is no need to add titrant externally in the Coulometric titration technique. Instead, the titrant is generated internally through an electrochemical reaction in the cell. The Coulometric technique is more accurate than the volumetric types and can detect water content in the range of 10µg to 100mg, much lower than that of volumetric titrators.

Manufacturers a nowadays moving towards a new technique called Automated titration. It automates traditional titration instruments to perform automatic functions such as sample preparation, analysis, and final result calculation. This speeds up the titration measurement, and the process does not require stopping for sample preparation. Both Volumetric and Coulometric types can be automated. 

Spectrophotometers

A spectrophotometer is a standard analytical instrument in the pharmaceutical industry. Its primary purpose is to measure the concentration of a solute in a sample solvent. This principle can then be used for many different applications, such as impurity detection or measuring the concentration of a particular active pharma ingredients – API. 

Typical applications of Spectrophotometers in the pharmaceutical industry include Raw material and Manufactured products. The United States Pharmacopeia (USP) and the European pharmacopeia (Ph. Eur.) provide guidelines about its usage.

This technique measures light intensity after it passes through the sample. Different particles present inside a sample affect the light’s intensity differently as it passes through it. The light intensity is measured as a function of wavelength. 

The selection of a particular wavelength depends on the required test and the type of test sample. When light passes through the sample, it falls on the detector. The detector detects the wavelength characteristics and converts them into equivalent results. The results are then displayed on display. Some Spectrophotometers also provide the provision of printing the results on paper. 

Commonly, two types of Spectrophotometers are used in the Pharmaceutical industry - Fourier Transformation Infrared (FTIR) and UV/Visible Spectroscopy. 

FTIR uses interferometry to calculate material characteristics. The final signal at the detector is the spectrum representation of the molecules of materials present in the sample. 

UV/Visible Spectroscopy uses light frequency in the visible or near-visible light region. It is generally used for detecting contaminants in the sample.

Dissolution Apparatus

Dissolution Apparatus is used to perform dissolution testing of a pharmaceutical product. This test is used to determine the release rate of the active pharmaceutical present in the final product. Commonly, this test is performed on Oral Solid Dosage Forms and acts as a final release inspection to ensure product quality and consistency among different batches.

In Dissolution Apparatus, specific test conditions are developed to test the drug. Acceptance criteria associated with these conditions are necessary to pass to qualify the test.

Dissolution Test Apparatus consists of more than one small vessel in which a motorized mechanical arm rotates. The product is placed in the vessel containing media, and a mechanical arm rotates inside a vessel for a specific period. The temperature controller monitors and controls the required temperature. Dissolution apparatus is also provided with auto dosage systems, which automatically dose the system at set time intervals. Some manufacturers also provide autosamplers, which take samples at set time intervals without human involvement.

There are different types of mechanical arms, such as Peddles and Basket types. The selection of each specific arm depends on the product type being tested.

Types of Dissolution Test Apparatus

Generally,, classification of Dissolution Test Apparatus is carried out according standards set by United States Pharmacopeia – USP. USP categorizes dissolution apparatus into seven different types, and include the following

· Paddle type

· Basket type

· Reciprocating cylinder type

· Flow through cell, paddle over disc type

· Rotating cylinder type

· Reciprocating disc type

Basket type and Paddle type are most commonly used dissolution apparatus for oral dosage forms

Weighing Balances

Weighing balances are primary and essential analytical instruments used in the pharmaceutical industry. They are used to weigh different ingredients and components of a product so that each product’s formulation is not compromised. 

There are two types of weighing balances used in the pharmaceutical industry – Analytical and Precision. 

Analytical Balances are much more sensitive and accurate than precision balances and can be effectively used in weighing smaller quantities. The analytical balances are very sensitive and can be easily affected by air currents present in the balance area. For this purpose, these balances are placed in an area with minimum chance of any disturbance. 

Precision balances are less sensitive than Analytical Balance, and they can measure the weight of larger quantities than the analytical balance. They are also less sensitive than analytical balances and are least affected by external factors, so no proper arrangement is required.

In the pharmaceutical industry, weighing scales are used in many departments for weighing applications, including the following.

QC/ QA: Weighing scales are regularly used in the QC section for measuring different quantities intended for performing the test. QA department uses it to perform a test on the different production processes.

Production Department: The production department uses a weighing scale for manufacturing products in Injectable, Oral Solid Dosage, and Liquid Section. Weighing scales are also used in the in-process lab of production departments for process monitoring by Production and Quality Assurance Personnel.

Raw Material Department: Raw material department uses weighing scales to dispatch a proper amount of material for the production process. Because pharmaceutical raw materials are costly, accurate record-keeping of dispensed material. Secondly, regulatory bodies require pharmaceutical manufacturers to keep records to prevent misuse of pharmaceutical materials.

pH meters

pH meters measure and classify a solution as acidic or basic. It measures the Hydrogen ion activity of a solution, and based on hydrogen ion concentration; the instruments classify the solution as acid or Basic. If there are more H+ ions than OH ions, the solution is acidic. On the other hand, if the concentration of H+ ions is more minor than OH ions, the solution is classified as Basic.

PH measurement is an essential parameter in the pharmaceutical industry's manufacturing and testing production process. Every manufacturing phase has a specific pH value, measured for verification purposes. If the pH value deviates from the specific required range, the pH value needs to be fixed, so that accurate product results are achieved. 

There are two types of pH meters used in the pharmaceutical industry – Benchtop and Portable type. 

Benchtop pH meters are placed on the table and cannot be easily moved. In addition to essential measurement, they have additional accessories such as a result printing option and memorizing different readings.

Portable pH meters are smaller in size and can easily be moved from one location to another, for example, in industries where field measurement becomes necessary, such as in Chemical or Water treatment plants. They contain only essential functions for measuring pH. They can also be used in place of Benchtop pH meters.

Buffer Solutions: Buffer solutions are standard solutions of known pH value and come in 4 and 7. They are used to calibrate or verify the pH meter is working. Because the pH value of buffer solution is known, deviation in the results can easily be indicated, which is then corrected for further application.

Hardness testers

Hardness testers are used to test tablet hardness during tablet compression. It detects the breaking strength of tablets. This test helps determine the tablet's durability during transportation and storage. A standard unit of hardness measurement = is Newton (N). Tablet Hardness test is considered a Non-Pharmacopoeial test, as any Pharmacopoeia provides no official information. Instead, it depends on the manufacturer to set its limits and different acceptance criteria.

Tablet hardness tester consists of two jaws, adjusted opposite to each other. The tablet is placed between these two jaws, which exerts a force on the tablet. The jaws are pressed against each other until the tablet breaks. The point at which the tablet breaks is the tablet's hardness.

There are two types of Hardness Tester – Automatic and Manual.

An automatic hardness tester is provided with motorized jaws, which move automatically against each other. The hardness tester also contains a display that shows the reading; when the test starts, jaws automatically move against each other with the tablet in between. When the tablet breaks, motorized jaws stop, and the display shows the hardness reading.

In manual type, the jaw moves manually with the help of a handle. The handle is rotated manually to move the jaw forward or reverse against the fixed block. Tablet is fixed in between the jaw and the fixed block. There are markings on the handle representing the hardness value. When the handle rotates, the jaw exerts a force on the tablet. At the instant tablet breaks, the handle is stopped rotating. The markings on the handle represent the hardness of the tablet.

Friabilitors

Friabilators are used to perform friability tests on a tablet and test tablet strength against mechanical pressure. The tablets should be uncoated for successful test execution.

Friability Test instrument consists of a rotating drum in which tablets are placed. The drum is rotated for a specific time, with tablets in it. After the test is completed, the conditions of tablets are analyzed. If the condition of the tablet is satisfactory, the test is considered to pass; else, the test is marked failed.

Some friabilators have more than one drum. Counter and alarm are also added as an accessory to the instrument. 

Incubators

Incubators are a medical instrument used in the pharmaceutical industry, commonly in the Quality Control lab, for testing microbiologic culture. They are used to create ideal and healthy environmental conditions for the culture to develop. The cultures are used in developing different drugs. These cultures are also used in testing procedure contamination monitoring in different pharmaceutical products.

Commonly, incubators are microprocessor-based which continuously monitors the temperature for automatic control. A fan blows hot air inside the incubator chamber to ensure an even temperature in the whole chamber. A heater is used to heat the chamber to desired temperature requirement. The temperature sensor placed inside the chamber measures the temperature reading.

When selecting incubators, some vital consideration needs to be addressed before selection. Some of them include the following.

Uniform Temperature Distribution: The incubator must have uniform temperature distribution throughout the chamber. Un-even temperature distribution will cause some samples to mature, while others will remain undeveloped. This creates inconsistent and faulty test results that are unreliable. 

Contamination Control: The incubator must include a system for contamination control because testing materials can cause contamination to the internal structure and other testing materials placed inside an incubating chamber. Commonly, contamination control is achieved by heating the chamber with a high temperature such as 100⁰C.

Record Monitoring: Regulatory bodies require the manufacturers to correctly record all the operating parameters and test results. Most quality incubators manufacturers include the record monitoring option in their manufacturing. This feature can record operating parameters, with the type of product being incubated.

Easy Operation: The incubator can be easily operated without any difficulty. All the operational commands such as Start, Stop, time interval, and temperature value can be performed without difficulty. It is achieved by quickly understanding the command, and the display should be easily identifiable and readable. Some manufacturers also include different language selections for regional operations.

About the author：

Muhammad Asim Niazi has a vast experience of about 11 years in a Pharmaceutical company. During his tenure he worked in their different departments and had been part of many initiatives within the company. He now uses his experience and skill to write interested content for audiences at PharmaSources.com.