D) FILLING PROCEDURE

D) Filling procedure

The filling process has been categorized as the filling of low density and viscosity liquids, filling of viscous liquids and filling of solids. Filling equipment has a reservoir to hold bulk product. The reservoir is connected to delivery tube to dispense product into container. A mean is provided for repetitively forcing a measured volume/amount through the orifice of a delivery tube. The accuracy and the precision of the machine filling of sterile liquids vary with the method. Therefore, a method is selected to provide the degree of accuracy and precision required by the nature of the product. The slightest excess is required in each container to provide for the loss that occurs at the time of the withdrawal of dose at the time of administration due to adherence of container content to the wall of container and retention in the syringe. Filling machines should be designed so that the part through which the liquid flows can be easily demounted for cleaning and for sterilization. These parts also should be constructed of non-reactive materials, such as borosilicate glass or stainless steel. Syringes are usually made of stainless steel, when the pressure required for delivery of the viscous liquid or large volumes would be useful for glass syringes.

Filling of low viscosity small volume liquid preparations

A liquid may be subdivided from a bulk container to individual dose containers more easily and uniformly than a solid. Mechanical subdivision of a mobile, low density liquid can be achieved with light-duty machinery. Certain fundamental features are found on all filling equipments for liquid preparations. The filling equipment has a reservoir to hold the bulk of the liquid preparation to be filled into containers. A means is provided for repetitively forcing a precisely measured volume of the liquid through the orifice of a delivery tube designed to enter the constricted opening of a container. The size of the delivery tube is governed by the opening in the container to be used, viscosity and density of the liquid and the speed of the delivery desired. The tube must enter freely into the neck of the container and deliver the liquid deep enough to permit air to escape without sweeping the entering liquid into the neck or out of the container. To reduce the resistance to the follow of the liquid, the tube should have the maximum possible diameter. Excessive force of delivery causes splashing of the liquid and troublesome foaming, if the liquid has a low surface tension. The delivery of relatively small volumes of liquids is usually obtained with pressure obtained from the strokes of the plunger of a syringe. The stroke of the syringe forces the liquid through a two-way valve that provides for an alternate filling of the syringe from a reservoir and delivery to a container. A drop of liquid normally hangs at the tip of the tube after a delivery. When the container to be filed is an ampoule, withdrawal of the tube without wetting the long restricted neck is almost impossible, unless the hanging drop of the liquid is retracted. Thus, a retracting device is designated as a part of the most filling machines.

Filling of low viscosity large volume liquid preparations

Sterile solutions of relatively low potency dispensed in large volumes (up to 1 liter) do not normally require the precision of filling that is required for small volumes of potent injectables. Therefore, the liquid is filled into the bottles by gravity, pressure or vacuum filling devices. Generally, gravity filling is relatively slow, but is accomplished with simpler means. A liquid reservoir is positioned above the filling line, with a hose connection from the reservoir to a shut-off device at the filling line. The shut-off device is usually hand operated, and the bottles are filled to graduations on the bottles.

The pressure pump filler often is operated semi-automatically and differs from the gravity fillers, principally in that the liquid is under pressure. It is usually equipped with the overflow tube connected to a receiver to prevent excess flow of the container. Vacuum filling is commonly used in faster filling lines for large liquid volumes because it is more acceptable for automation. A vacuum is produced in a bottle when a nozzle gasket makes a seal against the tip of the bottle to be filled. The vacuum draws the liquid from a reservoir through the delivery tube into the bottle. When the liquid level reaches to a level of an adjustable overflow tube, the seal is mechanically loosened and the vacuum

is released. Any liquid that had been drawn into the vacuum line is collected in a trap receiver and then returned to the reservoir.

Filling of high viscosity liquid preparations

The viscous, sticky or high density liquids require much more heavy machines to withstand the pressure required to dispense them in individual containers. Thus, compared to the plunger-syringe assembly for filling of low viscosity liquid, for heavy, viscous liquids, a sliding piston valve provides more positive action. Emulsion, suspensions and semisolid preparations often require specially designed filling equipments because of their high viscosity. To obtain a reasonable flow rate of the emulsion and suspension, high pressure must be applied or container with large openings must be used to permit the entry of large delivery tubes. Sometimes the jacketed tanks can be used to raise the temperature of the product to facilitate filling by lowering its viscosity. It is normally necessary to keep suspensions and sometimes emulsion, constantly agitated in the reservoir during filling so that the product remains homogeneous and each subdivided unit contains the required amount of drug.