Introduction
Tableting is a complex multi- stage process. It is the method of processing drugs into tablet dosage forms. These methods may be considered to consist of a series of steps (unit processes or operations).
The primary goals of tableting is to formulate tablets that are strong and uniform which would consequently pass quality Control tests when subjected to. The tablets must be chemically and physically stable for a long period of time. The tablet is also formulated to be pharmaceutically elegant and bioavailable.
Factors to Consider before Tableting
Several factors are being considered before tableting a drug which includes:
- Choice of excipients
- Area required for manufacturing of tablets
- Personnel required during manufacturing process
- Manufacturing equipments and machines
- Quality of raw materials used.
1. Choice of Excipients
Excipient is an inactive substance that is used in tableting to either increase the appearance or as a carrier. Formulation activities begin by identifying the excipients most suitable for a prototype formulation of drug followed by the levels these excipients needed depending on the prototype formulation.
Factors Influencing Choice of Excipients
These factors include:
- Excipients Functionality: Functionality is linked to the formulation and process. its assessed in the context of a particular formulation
- Excipients Grade: Excipient come in different grades and the grades are differentiated frequently by means of physical and chemical characteristics.
- Impurity Profile: This is defined as the materials other than the original raw material. They are also called concomitant components
- Formulation Design: Fewer ingredients are better because excipients are not completely inert, better economic efficiency and less probability of chemical and physical interaction between the active pharmaceutical ingredient and the excipient.
- Drug-Excipient and Excipient-Excipient Interaction: The excipient used should be inert. In other words, it should not react with the active pharmaceutical ingredients or the other excipients to be added. So the excipient selected should be tested for interaction with the drug or other excipients.
2. Area Required for Manufacturing
Pharmaceutical manufacturing is done in a highly controlled and regulated environment. The area of manufacturing should be large enough to contain the machines and personal space of the manufacturing personnel. The area is required to be neat and standard.
3. Personnel Required for Tablets Manufacturing Processes
These include:
- Supervision pharmacist/ production pharmacist
- Manufacturing chemist
- Analytical chemist
- Quality assurance manager
- Machine operators
- Mechanics
Pharmaceutical Tablets Manufacturing Processes
The choice of process of tableting depends on the drug properties or its intended use. The processes might be dry granulation, wet granulation or direct compartment. It also include the choice of compression method which depend on the machine available that is single punch ot multiple punches compression machine. The type of coating to be used is also selected depending on the nature of the tablet and technique of manufacture. then lastly the choice packaging process is also made depending on the content of the tablets and other factors.
4. Manufacturing Equipments:
The major equipments and machines for the manufacturing of tablets should be available and the choice of manufacturing process also depends on the type of machine and equipment available.
The needed equipments include the following:
- Measuring equipments: Weighing balance
- Size reduction equipments: hammer mill, roller mill etc
- Granulators
- Drying equipment: vaccum driers
- Tableting machines
- Coating equipments
- Packaging machines: blisters and strip packaging machines etc.
- Quality control equipments.
5. Quality of Raw Materials Used
Quality of raw materials used are assessed through method called QUALITY CONTROL. Quality control is a process by which entities review the quality of all factors involved in production starting from the raw materials.
All of the top pharmaceutical companies access the quality of their material before processing. Every pharmaceutical company is actually expected to do this.
Chemical and Physico-Chemical Testing of Pharmaceuticals
- Assays and chemical test
- UV/VI
- IR
- AAS
- HPLC
- GC
- IC
- ICP-MS
- Identification of active pharmaceutical ingredient (API) and impurities
- physical and Physico-Chemical determination
- pH, Viscosity, melting point, particle size, osmolality and osmolarity, flash point, loss on drying, limit test, heavy metal, ash, anions, residual solvent , volatile organic impurities, pharmaceutical technical procedures, disintegration , dissolution, hardness, friability, sampling and analyses of water.
Steps Involved in Tablet Formulation
- Weighing or dispensing of ingredients in the tablet formula
- Sizing of the particles
- Powder blending
- Granulation
- Drying and dry screening
- Tablet compression
- Coating of tablets
- Packaging
Techniques or Method Used in Tablet Formulation
1. Granulation
This is a unit operation in which small powder particles are gathered together to form agglomerate called granules. It is a size enlargement process. To achieve cohesion between particles we include substance called binders or granulating agents.
Granulation begins with initial dry mixing of necessary powder ingredients for uniform mixing
Phases in Developing Granules
a. Intra Granular Phase
Here, active pharmaceutical ingredient (s) (API) is added from the begining. It include mixing API, fillers and binders
b. Extra Granular Phase
This involves addition of the other excipients to the initial intra granulated components. Extra granular components include disintegrants, lubricants, glidants
Types of Granulation
Before you choose any granulating method preformulation studies is required to know the properties of the ingredients.
i. Wet Granulation
Wet Granulation exploit a granulation liquid phase called binders by formation of a wet mass by adhesion. It is the most widely used method of granulation.
Steps Involved in Wet Granulation
- Weighing out and homogenization of dry powders
- Wetting by binder solution: done by pouring, spraying and melting
- Wet screening: process of adding water to the screen to remove undersized materials efficiently.
- Drying of the finished product
- Mixing with disintegrants and lubricant
- Compressing of granules into tablets
ii. Dry Granulation
This process is used when tablets excipients have sufficient inherent binding properties. It omit some steps that are involved in wet granulation. It doesn’t involve liquid phased of adding/ mixing binders.
Steps Involved in Dry Granulation
- Weighing and homogenization of powders
- Mixing the powders together
- Slugging: pre- compression process for the formation of extra large tablets (slugs). The resulting slug are subsequently broken into granules.
- Dry screening: process of screening of solid materials of different sizes without aid of water.
- Lubrication and compression.
2. Direct Compression Method
This method or technique involve direct compression of powdered materials into tablets as the name implies without first modifying the physical nature of the materials itself by granulation. It is successfully applied when suitable excipients and suitable machines are available.
Steps Involved in Direct Compression
- Homogenization of API and excipients.
- Mixing powders of disintegrants and lubricants
- Compression.
Tablet Compression
Compression is done by either single punch or multiple station machine. Compression is the process that follows after preparation of granules (wet granulation) or slug in (in case of dry granulation) or mixing of ingredients( in case of direct compression). They are compressed to get the final product. Each tablet is made by pressing the granules inside a die, made up of hardened steel. The die is a disc shape with hole cut through the centre.
Types of Compression Machine
- Single punch/ single station/ eccentric presses
- Multi – station/ Rotatory press
SINGLE PUNCH is the simplest form. It consist of a die and a pair of upper and lowe punches. The lower punch is static. Single punch is referred to as stamping process because the compaction force is exerted only by upper punch.
MULTI-STATION is a mechanical device that has several toothing station which rotates to compress granules/ powder mixtures into tablets. It increases the output of tablets.
Stages of Tablet Compression
- Filling
- Metering weight adgustment
- Compression
- Ejection/ removal
Tablet Coating
Tablet coating is a process by which an essentially dry, outer layer of coating material is applied to the surface of a dosage form in order to confer specific benefits over uncoated variety.
Techniques of Tablet Coating
- Sugar coating
- Film coating
- Compression coating
- Micro encapsulation
Sugar Coating
It involves deposition of aqueous sugar solutions into the surface of the core tablet. Its one of the oldest form of coating.
Steps Involved in Sugar Coating
- Sealing products
- sub coating: include lamination and suspension
- Smoothing
- Colouring
- Polishing
- Printing
Film Coating
Film forming materials is deposited on the core tablets. It gives minimal weight increase,saves time and highly efficient.
Compression Coating
It involves fine dry granulation compressed into a tablet core of a drug. It is a dry coating process thus suitable moisture and heat sensitive drug formulations.
Micro Encapsulation
It involves the thin coating to a small particle of solids, liquids, or gases in a micron dimension . The difference between micro encapsulation and film coating is the size of particles to be coated and method used.
Packaging of Tablets
Packaging is the last process of tableting. Packaging is the science, art, and technology of enclosing or protecting products for distribution, storage, sales and use. Pharmaceutical packaging is the packaging process for pharmaceutical preparation. Choice of packaging depends on the content of the tablet and the country of use. The convenience of the end users is also considered.
Recent advances in packaging design , material and technologies mean that there is a wide variety of user friendly primary and secondary packaging options to choose from. The sole aim of packaging is to protect the content of the tablet.
Major Functions of Packaging
- PRODUCT PROTECTION: This depends on the nature of the tablet example for effervescent tablets that react vigorously with water, protection from moisture is particularly important. Tube is a better design feature to protect from humidity.
- CONVENIENCE AND CUSTOMISATION: Patient and consumers increasingly expect convenience in their lives and product. For older patients product packaging can be a significant barrier to assessing medicine. Design features can be incorporated into the packaging to make opening easier.
- SAFETY CONSIDERATIONS: Ease of opening and convenience must be balanced with appropriate design to ensure packaging is resistant to opening by children.
- PRODUCT IDENTIFICATION: Helps to identify the product type.
- BUILDING STRONG CUSTOMER CONNECTION: Packaging are designed to be attractive and elegant. this can be as advertisement and building strong customer connection. It used in transmission of information about the drug to the potential customers.
Types of Packaging Materials
- PRIMARY PACKAGING: Its the material that first envelops the product and hols it.
- SECONDARY PACKAGING: It is outside the primary packaging perhaps used to group primary packages together eg cartons, boxes
- TERTIARY PACKAGING: It is used to bulk package the secondary packaging for handling and shipping.
Quality Control of Tablets
Tablets are subjected to quality control assessments after compression to ensure the standard of the drug is maintained uniformly. Official test and non official tests are carried out.
Official Tests
The following are a list of Pharmacopoeial or official tests tablets undergo after manufacturing before being put to use.
- Content of API
- Weight Uniformity Test
- Content Uniformity Test
- Disintegration time test
- Dissolution test
Non Pharmacopoeial or non Official Tests
The following tests are unofficial tests carried out on pharmaceutical tablets after formulation before being put to use.
- Crushing strength test
- Friability test
- Tensile strength determination.