The Role of Dissolution Testing in Supplement Development

By Dr. Priyom Bose, Ph.D.Reviewed by Lily Ramsey, LLM

Dissolution testing plays an important role throughout the life cycle of a pharmaceutical product, i.e., from evaluating how quickly a compound dissolves into solution in controlled conditions to assessing its stability.¹

This is a vital analytical test used for quality control (QC) during various phases of supplement development.²

​​​​​​​Image Credit: Aria Armoko/Shutterstock.com

Purpose of Dissolution Testing

Dissolution testing is performed for different kinds of products, including those ingested orally, such as tablets and capsules, and topical formulations applied as ointments and gels.³ Manufacturers depend on this analytical test to assess batch-to-batch stability and consistency.

The dissolution rate is the speed at which a substrate dissolves in a media or solvent.⁴ As this rate indicates the bioavailability of the supplement, scientists estimate the dissolution rate to understand whether a new formulation has acceptable bioavailability.⁵

Regular dissolution rate monitoring helps detect potential variations in batches that may affect the efficacy of the supplement. This QC strategy helps maintain the integrity and safety of the supplement throughout its shelf life.

Dissolution testing helps optimize the rate of bioactive component release of a given formulation.⁶

Any modifications in the physical properties of the active ingredients of the supplement are detected through this test.

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Standard Dissolution Testing Methods

Both scientific and regulatory principles are considered while developing a dissolution method. Efficient dissolution testing methods must have low variability and high reproducibility.⁷

In industrial or laboratory settings, dissolution testing methods are selected based on the molecular characteristics of components and the intended route of supplement administration. In the case of solid supplement forms, the industry-standard dissolution testing methodologies are USP Apparatus 2 (Paddle) and the United States Pharmacopoeia (USP) Apparatus I (Basket).

Other available dissolution testing includes USP 3 (Reciprocating Cylinder), USP 4 (Flow-through-Cell), USP 5 (Paddle-over-Disc), USP 6 (Rotating Cylinder), and USP 7 (Reciprocating Holder or Disc). Typically, variable, immediate, and extended releases of bioactive compounds are tested using USP 2 paddles.⁸

Dissolution testing methods have advanced through the advent of innovative new instruments, novel dissolution media, and methods. Currently, the combination of biorelevant dissolution testing and physiologically based absorption modeling (PBAM) has enabled the prediction of in vivo performance of the supplements.⁹

Automated dissolution systems have significantly improved accuracy and data processing.

The advanced software allows the storage of all data, i.e., experiment protocols and results, and offers built-in data integrity and ease of regulatory compliance.

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Factors Affecting the Dissolution Rates of Supplements

The dissolution rate is attributed to the degree of interaction between the supplement components and the dissolution medium.⁵ If the intermolecular force between supplement molecules is prematurely minimized, the dissolution process significantly speeds up.

Excipients are essential inactive components in supplements that are used as binders, disintegrants, lubricants, etc.¹⁰ For example, magnesium stearate functions as a lubricant and moisture repellent for capsules and tablets.

Excipients are added in a formulation to improve the dissolution rate of the product. Physicochemical parameters, surface area particle size, zeta potential, and water content or hygroscopicity are important parameters that affect the dissolution rate of the final product.¹¹

Some key parameters considered to improve the dissolution rate of a supplement are as follows:

1. The size and distribution of excipients influence the mixing characteristics, flow properties, and dissolution rate of the supplement. A smaller particle size elevates the supplement’s bioavailability and dissolution, while a larger particle size improves flow properties.
2. Dissolution media mimic biological environments. Typically, the pH strength of the media ranges between 1.2 and 6.8, as per USP guidelines.
3. Specific USP apparatus must be selected for dissolution testing based on the test purpose or specific active ingredients.
4. The porosity of excipients influences the supplement’s capacity to absorb or release moisture. It affects the stability and performance of the final product. A higher porosity makes supplements more moisture-sensitive but improves their flow properties and compressibility.
5. The bulk densities of components impact the supplement product by affecting compressibility and flow properties. A higher bulk density elevates flow properties, while a lower bulk density improves compressibility.
6. The addition of weak water-soluble components in supplement formulation decelerates the dissolution rate.
7. A weak interaction between excipient and supplement (active compound) molecules enables the maintenance of the dispersion state of bioactive compounds in a carrier. A higher interaction energy between active molecules and excipients significantly contributes to drug dissolution.
8. Excipients with high hygroscopic properties influence the stability of the final product

Regulatory Requirements For Dissolution Testing

Dissolution testing is performed to evaluate the therapeutic efficacy, bioavailability, and bioequivalence of active pharmaceutical ingredients (API). As stated above, this analytical method is popularly used for QC involved in different production phases.

Regulatory bodies, such as the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), have provided detailed guidelines for the comparison of dissolution profiles.¹²

These guidelines focus on ensuring generic formulations are bioequivalent to their branded counterparts, offering similar therapeutic outcomes irrespective of the manufacturer.

The similarity factor f2, which quantifies similarities between two dissolution profiles, is used as the statistical tool for comparing dissolution profiles.¹³ If f2 value of a supplement ranges between 50 and 100, it implies that the two dissolution profiles are similar. However, this approach is not reliable when dissolution data is highly variable.

Both the FDA and EMA sought to address the limitations of f2 metric via alternative statistical methods, such as model-dependent and -independent approaches.

These methods considered confidence interval derivation through bootstrap techniques. It also applies multivariate statistical distances (e.g., Mahalanobis distance).

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References

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10. van der Merwe J, Steenekamp J, Steyn D, Hamman J. The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability. Pharmaceutics. 2020;12(5):393. doi: 10.3390/pharmaceutics12050393.
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13. Diaz DA, et al. Dissolution Similarity Requirements: How Similar or Dissimilar Are the Global Regulatory Expectations? AAPS J. 2016;18(1):15-22. doi: 10.1208/s12248-015-9830-9.