In this article we will discuss about manufacturing process. Documentations, Requirements and other formalities to start solid dosage form is similar as starting manufacturing company
Solid Dosage form is well accepted and most popular doasge form in pharmaceutical industry. Accuracy in dose and easy to take like advantage give it popularity among professionals and patients. Today we are going to discuss about manufacturing of solid dosage form i.e. Tablet and Capsule.
Non Technical Staff:
- Machine Operators
- Mixing, Granulation and Drying Section
- Tablet Punching Section
- Coating (Film Coating and Sugar Coating) Section
- Capsule Filling Section (In case of Capsule)
- Packaging Section
- Weighing Machines and Testing Equipments ( E.g. Electronic Balance, Hardness tester, Friability and Disintegrated Test Apparatus, tablet inspection units, Dissolution test apparatus etc)
- Disintegrator and Shifter
- Mixer (Mass/Rapid/Planetary Mixer)
- Drier (Trey/Fluid Bed Drier)
- Rotatory (Tablet Compression Machine) – Single or Multi Punch
- Punches and Dies (As per tablet Size/s)
- Packaging machines (Blister/Strip/Alu-alu etc) and Testing Equipments
- Coating and Polishing Pan (In case of Coated Tablets)
- Capsule Filling Machine
- Dispensing of Ingredients
- Milling & Granulation
- Final Blending:
- Tablet Compression
Three Processes are used to manufacture tablet dosage form:
- Direct Compression
- Wet Granulating
- Dry Granulating
Direct Compression Method: This method is used for tablet compression only if powder/s is easily compressible and doesn’t require any additional requirement for compression. All powders are mixed and directly compressed into tablet punching machine for making a tablet. Powdered should be blended together and should remain in mixed form.
Wet Granulating Method: Widely used method for making tablets. If powders used are not easily compressible or floppy in nature or don’t mix well then wet granulating process is used. Wet granulating method follows following steps:
- Mixing of active ingredients and excipients
- Preparation of binding material
- Addition or mixing of mixed powders and binding solution
- Sieved or milled to convert into granules
- Drying and Sieve again
- Mix disintegrant, glidant and lubricant in to it
Dry Granulating Method: If the material used is sensitive to heat or volatile in nature then we have to compress tablet without use of heat and solvents. There are two basic procedures used in dry granulating method. One is to form a pack or compact by compression and then sieved or milled to convert into granules. In dry granulation, one method is to recompress powder into slugs and milled to form granules and second method is to form compacts through pressure. Compaction of powder is accomplished by rolling powder under pressure.
Method used for manufacturing tablet is depended at raw material nature used for making tablets. Wet Granulating Method is widely accepted and used to compress raw material into tablet form.
A tablet contains many ingredients other than active ingredient/s to manufacture a good quality tablet. These ingredients are known as Excipients. These excipients are in-active and neutral in nature and don’t have any medicinal property so don’t show any effect or side effect in body. Quantity and nature of active ingredients vary product to product and manufacturing method to method. A particular formula is prepared and keeps safe for future purpose for conversion of a particular active ingredient into tablet form. This formula contains adequate quantity of excipients to be added to smoothly convert a molecule into tablet form. This formula is known as Master Formuls Record. Whole manufacturing process is noted down in a record known as Batch Manufacturing Record (BMR). BMR is prepared batch wise and has to keep at safe place for future reference. A Particular number is provided to a Batch for maintaining record and samples known as Batch Number. BMR record should be duly maintained and signed by authorized person (Supervisor or Manufacturing Chemist). At every step of manufacturing, quality assurance team will inspect whole process and will check for quality & accuracy purpose. Quality Control section test for accuracy of all parameters as per reference book.
Procedure for Tablet manufacturing:
- Dispensing: Each ingredient including active ingredient/s should be accurately dispenses as per dose. It is one of the critical steps any type of formulation. Weighing and measuring should be done under technical supervision.
- Sizing: If all ingredients are of equal size, it becomes easier to mix all of them. Sizing is an important part in tablet manufacturing. Reduce all ingredients to equal size for better flow property and easy mixing.
- Blending: Blend all powders to make a uniform and homogeneous mixer.
- Formulation: Mix this mixture with binding agent.
- Milling: Now above formulation passed through mills or sieves to form granules.
- Drying: Granules need to be dried for a particular time period in trey dry or fluid bed drier.
- Milling: Again pass through this mixture into mills and sieve it.
- Final Blending: Blend above granules finally with disintegrants, Lubricates and glidants.
- Rotary Machine: Next step is to compress these granules into Tablet Form. Rotary machine contains punch and die. Size and shape of punch and die may vary according to your need. Compression is crucial for tablet manufacturing. It should not be low or high. If it will be low, tablet will not have hardness. If compression is high then tablet dissolution time will be affected. Granules or powder is flowed toward dye; fill the space obtained by vacuum in die. After filling of die, punch compression is obtained to convert powder or granules into tablet.
- Coating Pan: If tablets need to be coated then a coating material is prepared and sprayed at tablets in coating pan till desired coating film is obtained.
- Packaging: Now tablets are packed into pre-defined packaging material.
Tablets Defects that should be consider during Manufacturing:
- Weight Variation
- Friability Variation
- Capping and Molting
- Sticking and Picking
- Double Press
Test during and after Manufacturing:
- Weight Variation
- Dissolution Time
- Friability Testing
Why Granules is more beneficial than powder form:
- Improve powder flow property and create uniformity in dosage form
- Improve Compressibility
- Reduce fineness
- Control Powder tendency to segregates
- Control Density
Disadvantage of Powder Forms:
- Poor Flow Property
- Capping and Laminating Property
- Don’t mix well
- Dust Formation
- Difficult to handle
Hard Gelating Capsule Filling Process:
Few steps of capsule filling process are same as Tablet manufacturing process. Powder has many disadvantages as compare to granules, so in capsules filling we require granules or pallets (about pallets we will discuss in other articles) but powder is also filled into capsule body. Till Granulation, whole process is same as in case of tablet manufacturing process. Temperature, moisture and humidity of area where capsule is going to be filled should be controlled with the help of air conditioner and de-humidifier. Capsule shell is sensitive to moisture and heat. So handle it with caution.
Principles of Capsule Filling Machines:
- Positioned all incoming capsules into upright position
- Separate Cap and Body of Capsule Shell
- Attained Pre-determined Volume
- Fill powder/granules/pallets in Capsule shell body
- Remove excess material
- Rejoined Cap and Body of Capsule Shell
- Eject capsule from machine
- Polishing of capsule shell
- Developing and preparing the formulation and selecting the capsule size
- Filling the capsule shells
- Capsule sealing (optional)
- Cleaning and polishing the filled capsules
Types of Capsule Filling Machines:
- Hand Operated Capsule Filling Machine
- Semi-Automatic Capsule Filling Machine
- Automatic Capsule filling Machine
Hand Operated Capsule Filling Machine:
An operator is required to handle whole process manually. Operated is required to organize capsules in correct position and fill in tray having 200 to 300 holes and placed at bed having same holes. Separate caps from body with the help of cam handle, accurately positioned powder tray to fill body with drug, use pin tray to press filled powder and fill more powder for accurate dose, remove powder tray after complete filling. Replace cap handling tray and operate handle to re-joined capsule shell, remove loading tray and collect filed capsules. Approximately forty thousand to sixty thousand capsules can be filled in eight hour shift.
Hand operated machine is consisted of bed having holes and cap handling tray, a loading tray, A powder Tray, A pin Plate, A sealing plate having rubber top, A lever, A cam Handle.
Semi Automatic Capsule Filling Machine: In semi automatic capsule filling machine, operator require to move rings (Capsule holder rings) from rectifier to the filling and closing section. Production capacity of semi-automatic capsule could be 25000 capsules per hour which is two lakh capsule in eight hour shift.
Automatic Capsule Filling Machine:Automatic machine are divided into two categories: Continuous and Intermittent operations. In Intermittent operation, machine is divided into two segments. Each segment indexes from each machine function; rectifying, fill, tamp, close and eject. In continuous operation, machine is work continuously from capsule pouring to capsule filling.