Role of Excipient on the Behaviour of Dissolution

Introduction:  

Pharmaceutical excipients are inactive ingredients, other than the active pharmaceutical ingredient (API), added to drug formulations to enhance stability, bioavailability, and patient acceptability, and to aid in manufacturing. These substances are included in drug products alongside the active ingredient for the purpose of long-term stabilisation, to aid the manufacturing process, and to address active substance concerns, such as facilitating powder flowability or non-stick properties.

The selection of suitable and proper excipients depends upon the route of administration, the dosage form, and the active ingredient, among other factors. Excipients play a crucial role in ensuring the quality, safety, and efficacy of pharmaceutical products. Excipients can include diluents, binders, disintegrants, lubricants, colorants, sweeteners, and preservatives. They are essential for achieving the desired drug properties, such as solubility, stability, and release rate. Though they do not have therapeutic effects, excipients play a critical role in determining the dissolution behaviour of the final dosage form.

In this topic, we will focus on the role of different excipients on the behaviour of dissolution of finished dose products by examining how different excipients play a key role in dissolution, in both positive and negative ways. As we know, excipients are classified into different categories according to their use. Excipients can be used as fillers, disintegrants, lubricants, colouring matters, antioxidants, preservatives, adjuvants, stabilisers, thickeners, emulsifiers, solubilisers, permeation enhancers, flavouring and aromatic substances, etc.

For a comprehensive guide on excipient selection criteria, compatibility testing, and regulatory considerations, please refer to our detailed post on Understanding Excipients in Pharmaceuticals.

Key Excipient Categories and Their Impact on Dissolution

1. Disintegrants

Sodium starch glycolate, croscarmellose sodium, and crospovidone are the excipients which are considered disintegrants. These excipients help in enhancing the breakup of tablets into smaller fragments upon contact with gastrointestinal fluids. This action increases the surface area of API and thus improves the disintegration rate and dissolution rate. It is necessary to use them in proper proportions. The overuse or underuse can decrease or excessively increase the disintegration, and it may negatively impact the rate of dissolution.

2. Binders

There are different types of binders used in formulations as natural and synthetic binders. Starch, gelatine, and gums are natural binders, while povidone, polyethene glycol, and hydroxypropyl methyl cellulose are synthetic binders. Binders are used to hold the formulation components together. Binders improve the strength of the tablet and avoid breaking or crumbling during processing. They help to form a uniform granulation. It is important to choose the right binder for a formulation, as a strong binder leads to the formulation of tablets which are hard and require more time to disintegrate. Strong binders reduce the porosity, and the rate of penetration of water is slowed down; thus, the rate of dissolution is hampered. On the other hand, a weak binder can fasten the rate of disintegration and improve dissolution. Thus, the selection of the binder plays an important role in dissolution, and if not optimised, it will have an impact on dissolution.

3. Lubricants

Lubricants are used to improve the flowability of the material by avoiding sticking during manufacturing. Magnesium stearate is the most widely used lubricant. It shows excellent lubrication properties. Many lubricants are hydrophobic; they repel water. This can hinder the disintegration and dissolution of tablets. Even 0.5% and 1% can change the dissolution pattern drastically. Alternative lubricants like sodium stearyl fumarate or hydrophilic lubricants may be used to improve dissolution.

4. Fillers or Diluents

Lactose, starch, and cellulose are classified as diluents, which are used in the formulation. Soluble as well as insoluble fillers are used in the formulation. These are used in bulk quantities and called fillers. Lactose and mannitol impact the hardness. Calcium phosphate can be used as a filler because of its ability to absorb water and its swelling properties. Fillers can increase the surface area of the tablet, leading to faster disintegration and dissolution. Fillers can impact the porosity of the tablet, which in turn affects the rate at which the drug dissolves.

5. Surfactants

Surfactants are used to improve the solubility of very poorly soluble drugs, and they help in the dissolution of drug products. Surfactants are used as wetting agents. Poly(vinyl alcohol), as well as Tween 20, Tween 80, sodium deoxycholate (SDC), and sodium dodecyl sulphate (SDS), and sodium stearate were used as surfactants. Surfactants can form micelles and improve drug solubility. Surfactants prevent crystallisation and help to stabilise the amorphous form of a drug, and help improve dissolution rate by maintaining a higher concentration of dissolved drug.

Selecting a proper concentration of surfactant is a crucial thing as it also potentially impacts negatively on dissolution rate if a high concentration of surfactant is used. In some cases, it leads to poor correlation to in vivo studies. Surfactants may form complexes with the drug and thus hinder the drug release. In short, surfactants are valuable tools in dissolution studies, particularly for poorly soluble drugs, but their use requires careful consideration of their effects on solubility, wettability, and drug release kinetics.

6. Coating Agents

Different types of coating agents are used in the pharmaceutical industry. Hydroxypropyl methylcellulose (HPMC), ethyl cellulose, Eudragit, shellac, and various sugar-based coatings like sucrose, glucose, and maltodextrin are generally used for coating purposes. These excipients are used to do taste masking, protecting tablets from moisture, and for easy handling, and most importantly, for controlling drug release in different types of formulations.

Enteric coating of Eudragit avoids exposure to the acidic medium in the stomach and allows drug release in alkaline media by protecting the acid-sensitive drug. Polymeric excipients can control the rate of drug release and are used in extended-release or sustained-release formulations. Water-soluble and water-insoluble polymers create a matrix which controls the dissolution rate over a period. Coating is generally used either to improve or to retard the dissolution as per the therapeutic requirement. Film coating or immediate release coating is designed to dissolve rapidly after swallowing, releasing the drug quickly for immediate absorption. The thickness of the coating also plays an important role in drug release during extended-release formulations. The higher the thickness, the slower the drug release. It is important to select the right coating material, the percentage of coating, and the process of coating for optimum drug release.

Conclusion:

The selection of excipients is very crucial for optimising the dissolution of drugs in solid oral dosage forms. It is important to understand the mechanism of excipients which affect the drug release. Each category of excipients, from disintegrants that break tablets apart to coating agents that control release, plays a specific and vital role in determining how effectively a medication delivers its therapeutic benefit.

The dissolution behaviour of a dosage form is rarely determined by a single excipient. Rather, it emerges from the complex interplay of multiple components working together. Understanding how each excipient type influences dissolution, whether through enhancing water penetration, controlling disintegration, or modifying release kinetics, is essential for developing pharmaceutical products that achieve optimal therapeutic outcomes.

FAQ’s:

Reference:

• Paus, Raphael, et al. “Influence of Excipients on Solubility and Dissolution of Pharmaceuticals.” International Journal of Pharmaceutics, vol. 485, no. 1-2, Elsevier BV, Mar. 2015, pp. 277–87, https://doi.org/10.1016/j.ijpharm.2015.03.004.
• ‌van, et al. “The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability.” Pharmaceutics, vol. 12, no. 5, Multidisciplinary Digital Publishing Institute, Apr. 2020, pp. 393–93, https://doi.org/10.3390/pharmaceutics12050393.