Pharmaceutical Excipients

Pharmaceutical excipients are compounds normally included in a tablet besides the active ingredient. Their role is to ensure that tablet manufacturing processes can run smoothly, resulting in high-quality tablets without any technical issues. Excipients are categorized into different groups based on their main functions. However, one excipient can affect the tablets or powder in various ways, and many excipients can serve multiple purposes, making them multifunctional. The functions of these excipients are detailed in the following sections:

Filler

Example of substances: Lactose, Sucrose, Glucose, Mannitol, Sorbitol, Cellulose, Dicalcium phosphate dihydrate, Calcium carbonate.

In order for a tablet to be handled effectively, it must be of a suitable size, which requires meeting a lower limit in terms of powder volume and weight. Therefore, when dealing with a low dose of a potent drug, it’s necessary to add a filler to increase the bulk volume of the powder and thus the size of the tablet. However, a filler or diluent is not necessary when the drug dosage is high.

The requirements that the ideal filler should meet include:

  • Chemically inert.
  • Nonhygroscopic.
  • Biocompatible.
  • possess good biopharmaceutical properties (e.g. water soluble or hydrophilic).
  • possess good technical properties (such as compactability and dilution capacity).
  • Cheap.

Since a single substance cannot fulfill all these requirements, various substances have been employed as fillers in tablets, primarily carbohydrates, but also some inorganic salts.

Lactose is the most commonly used filler in tablet formulation. It has good properties as a filler, such as being an inert compound that does not react with most drugs and being non-hygroscopic. Moreover, it dissolves readily in water.

Lactose has two types: crystalline and amorphous. Crystalline lactose can be formed by precipitation and can be either α-lactose (a hydrous form) or β-lactose (an anhydrous form), depending on the precipitation conditions. Crystalline α-anhydrous can be prepared by thermal treatment of α-lactose monohydrate. Anhydrous lactose has an advantage over its counterpart as it circumvents the Maillard reaction. However, the anhydrous form can pick up moisture when exposed to elevated humidity.

Spray-dried lactose or amorphous lactose is prepared by the spray-drying of a lactose solution (giving completely amorphous particles) or a suspension of crystalline lactose. It is currently being used for direct compaction due to its better compactability.

Disintegrant

Example of substances: starch, cellulose, cross-linked polyvinylpyrrolidone, sodium starch glycolate and Sodium carboxymethylcellulose.

A disintegrant is crucial to ensuring the breakup of the tablet into smaller pieces for rapid drug dissolution. This process starts when the tablet comes into contact with a liquid. The primary goal of the disintegration process is to produce a large surface area to speed up the dissolution of the drug. This process can be done in two steps:

First, the liquid wets the solid and penetrates the pores of the tablet, leading to the breakup of the tablet into granules. In the second step, the granules break down into smaller particles because they contain the disintegrant (fig.1).

Fig. 1: Illustrates how a disintegrant work as a pharmaceutical excipient
Fig. 1: Illustrates how a disintegrant works as a pharmaceutical excipient.

Binder

Example of substances: cellulose, methylcellulose, polyvinylpyrrolidone, polyethylene glycol, gelatin, hydroxypropyl methylcellulose, sucrose and starch.

A binder is added to the powder mixture of the tablet to ensure that the granules and particles compact together and form a tablet with suitable mechanical strength. The binder can be classified into two categories:

  1. As a dry binder, it is used in the wet granulation process during ingredient mixing before wet massing. Moreover, it is used in the dry granulation process when ingredients are mixed before compaction (slugging or roller compaction).
  2. As a solution binder, it is used in wet granulation during wet massing.

Glidant

Example of substances: colloidal silica, magnesium stearate, and talc

The function of a glidant is to enhance the flowability of powder and granules. Glidants are added to powder for direct compaction and also to granules before tableting to ensure there are no weight variations and to achieve high-speed production.

The substances, act as glidants by adhering to irregular surface particles, making them more rounded and reducing friction between particles, thereby improving flowability.

Lubricant

Example of substances: magnesium stearate, stearic acid, polyethylene glycol, sodium lauryl sulfate, sodium stearyl fumarate and liquid paraffin.

The function of the lubricant is to reduce the friction between the tablets and the walls of the die cavity during tablet ejection. Lubrication is achieved mainly by two mechanisms:

  • Fluid lubrication: a layer of fluid separates the two surfaces from each other, which will reduce the friction.
  • Boundary lubrication: A very thin film of lubricant particles separates two solid surfaces, often only a few molecular layers thick. In this scenario, the nature of the solid surfaces plays a crucial role in affecting friction.

Reference:

  • Aulton, M. (2018). Aulton’s pharmaceutics, the design and manufacture of medicines. Edinburgh. : Elsevier.