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Filling And Sealing Of Parenteral

Filling of liquids:
Liquids can be easily and uniformly filled from the bulk container into the individual dose container.

Filling of small volume:
Small volumes are generally filled into the ampoules or vials. For filling of small volumes of liquid generally hypodermic needles and syringes are used which deliver the liquid into the container by the stroke of plunger of the syringe.

Filling of large volume:
Sterile solutions of low potency are dispensed in large volume. For filling of large volumes of sterile solutions generally gravity filling, pressure filling and vacuum filling are used.

Gravity filling:
In this, the reservoir of sterile solution is kept above the filling line having a connection between the reservoir and shut-off device at the filling line. The shut-off device operated manually and it stops the entry of liquid after filling of container or bottles to the graduations on the container.

Pressure filling:
In this, the filling of sterile solution is assisted by the pressure. This is equipped with a overflow tube connected to a receiver to stop excess filling of the container.

Vacuum filling:
It is generally used for large liquid volumes because it can be made automated. In this, a vacuum is created in the bottle when a nozzle gasket makes a seal against the lip of the bottle to be filled.
Then the vacuum draws the liquid from the reservoir through delivery tube into the bottle to be filled. When the liquid reaches to the adjustable overflow tube then seal is loosened and vacuum is released.

NOTE: The filling is done always in slight excess to avoid spoilage that occurs during administration due to adherence to the wall of bottle and retention on the syringe. The excess volume is given in USP.

Filling of emulsion and suspension:
Due to high viscosity of suspension and emulsion these are required specially designed filling equipments. To obtain adequate or uniform flow rate, high pressure and bottle with wide mouth are required. Sometimes, jacketed reservoir tanks are used to increase the temperature of liquid to decrease the viscosity. Generally emulsions and suspensions are stirred continuously in reservoir tank during filling for uniform distribution of drug in every filled container or bottle.

Filling of solids:
Sterile solids are more difficult to fill into the individual container as compared to sterile solutions. The flow rate of solid from the reservoir into the final container tends to be slow and non-uniform especially if solids are very fine. Containers having wide mouth are used for filling sterile solids because flow rate is slow and risk of loss is present due to falling of the solids.
Sterile solids can be filled into the final container by individual weighing. A scoop (like spatula)can be used that holds a volume approx. equal to the weight required, but finally weighed on the balance. This is a slow process.
When sterile solids are generally free-flowing then machines may be used for delivery of solid into the final container. These machines measure and deliver a volume of sterile solid approx. equal to weight required.
Another type of machine used for delivery of free flowing sterile solids uses augar in the funnel shaped hopper and shape & size of the augar can be adjusted to deliver a regulated volume of the solid into the container.
In another machine, a adjustable cavity in rim of filling wheel is filled by the vacuum as the wheel passes under the hopper. The contents are held by the vacuum until the cavity is inverted over the container when a jet of sterile air discharges the sterile solids. This machine dispenses dry solids which flow less freely.

Sealing of ampoules:
Sealing should be done in aseptic area adjacent to the filling area.

Sealing is of two types:
Tip sealing;
It is done by melting the sufficient glass at the tip of ampoule neck to form a bead and close the opening.
Pull sealing:
• It is done by heating the neck of a rotating ampoule below the tip and then pulling the tip away to form a small capillary to being melted closed.
• Pull sealing is slower process but it is more reliable than tip sealing.

• Powder ampoule or other having wide mouth opening should be sealed using pull- sealing.

Sealing bottles, cartridges and vials:
Glass or plastic vials and bottles are sealed by closing the opening with a rubber closure. The closure must be inserted as soon as possible after filling to avoid contamination of the content of container. Closures are inserted mechanically by high speed processing. When closures are inserted by machines then surfaces of closure should be halogenated or coated with silicone to reduce the friction. Rubber closures are held in position by means of the aluminium caps. The closure can not be removed without destroying the aluminium cap or it is tamperproof. It may be single aluminium cap/ double or triple aluminium caps. Single aluminium cap can be inserted using hand crimper and double or triple aluminium cap required greater force for crimping.

Filling and sealing of infusion bottles:
Infusion bottles are filled and sealed by blow fill and seal technology (BFS). In this technology, the container is formed, filled and sealed in one continuous, automated process. The basic concept of this technology is that a container is formed, filled and sealed in one process without human interference.

The BFS involves following steps:
Parison extrusion:
Pharmaceutically grade plastic resin is vertically heat extruded through a circular throat to form a hanging tube called parison.

Container moulding:
Extruded tube is then enclosed within a two part mould and tube is cut above the mould.

Container filling:
The mould is transferred to filling zone, where filling needles are lowered and filled the mould

Container sealing:
Filling needles are removed and secondary top mould seals the container.

Container discharge:
The product is discharged to non-sterile area for labeling, packaging and distribution.