Steve Byrn and David Engers
Improved Pharma
Feb. 11, 2026

Improved Pharma has recently expanded its dissolution capabilities by installing a fully automated Agilent 708-DS dissolution apparatus paired with the 850-DS autosampler. This capability enables highly controlled, reproducible, and information-rich dissolution testing that supports modern pharmaceutical development—from solid-state understanding and formulation optimization to stability and lifecycle management.

The value and speed of dissolution testing increase dramatically with automated equipment where temperature control, hydrodynamics, vessel alignment, and sampling timing are tightly controlled. Automation reduces operator variability, enables greater sampling efficiency, particularly over extended time periods, and allows dissolution experiments to be interpreted mechanistically rather than empirically. Automation also enables high-resolution profiles that are critical for detecting subtle differences in formulation composition and in some cases solid-form changes.

This system is particularly powerful for:

  • Formulation screening, where inactive ingredients, including coatings, and polymorphs, salts, cocrystals, or amorphous forms, may influence drug substance release
  • Stability studies, detecting changes in product release due to stressed conditions and associated with physical or chemical transformation
  • Process development, troubleshooting, and scale-up, especially when combined with small-scale manufacturability trials

The dissolution system together with Improved Pharma’s ultra-performance liquid chromatography (UPLC) and liquid chromatography-mass spectrometry (LC–MS) platforms allows direct correlation between release behavior, assay, and impurity profiles. This integrated approach enables rapid, data-driven decision-making.

Dissolution as a Unifying Measurement in Pharmaceutical Development

With modern automated systems, dissolution testing fulfills a fundamental role in the development of pharmaceutical solid dosage forms. Unlike most analytical techniques, dissolution brings together solid-state form, formulation design, manufacturing critical process parameters, and stability into a single, regulator-accepted measurement. Dissolution testing offers a practical tool to assess these complex material-formulation relationships. Dissolution, especially when facilitated by the automated system used at Improved Pharma, can help provide a deeper understanding of the factors that influence release from the drug product during a dissolution experiment.[1]

At Improved Pharma and predecessor, SSCI, Inc., dissolution is viewed not simply as a quality control test, but as an essential tool to achieve the target product profile that accelerates development and helps avoid late-stage surprises. This philosophy is grounded in decades of solid-state chemistry experience [2-5], where dissolution has repeatedly proven to be sensitive to changes in the components, composition and manufacturing of pharmaceutical drug products.

Dissolution as a Solid-State Diagnostic Tool

One of the recurring themes in solid-state chemistry is that different solid forms can exhibit dramatically different dissolution behavior, even when chemically identical. Polymorphs, hydrates, solvates, salts, cocrystals, and amorphous forms can all alter dissolution rate and extent of release, which in turn affects bioavailability. In addition, dissolution behavior can be influenced by surface changes and interfacial phenomena that can be detected by dissolution studies.[6]

Dissolution testing often provides the first practical indication that a solid-state transformation impacting product release has occurred. Subtle polymorphic conversion, partial amorphization, or desolvation events may not immediately trigger specification failures in assay or impurity testing, but they frequently manifest as changes in dissolution behavior. For this reason, dissolution has long been emphasized as a critical tool for detecting solid-state risk during early formulation development and during scale-up.

Stability, Manufacturing, and Lifecycle Risk Management

Recent regulatory practice increasingly uses dissolution as a primary comparator in post-approval change management, including site transfers, scale-up, and continuous manufacturing transitions. In these cases, dissolution profiles serve as a practical bridge between development knowledge and commercial control strategies. Dissolution testing is also routinely incorporated into stability programs because it is sensitive to both physical and chemical changes that affect drug release. Polymorphic transitions, hydrate formation or loss, excipient interactions, and particle growth can all alter dissolution profiles during storage. From a manufacturing perspective, dissolution is equally valuable for troubleshooting variability arising from blending, granulation, compression, coating processes, or matrix systems. Because dissolution integrates multiple material and process variables, it often reveals root causes that are not apparent from isolated physical measurements. This makes dissolution a cornerstone tool for lifecycle management and post-approval change control.

Regulatory Importance

From a regulatory perspective, dissolution answers a critical question: will patients see consistent drug exposure despite formulation, manufacturing, or site changes? This focus aligns directly with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q6A and M9 expectations that manufacturers understand and control the solid form and release behavior of their products. Thus, dissolution testing plays a central role in understanding formulations during drug development and establishing critical quality attributes (CQA). Regulators are increasingly emphasizing discriminatory dissolution methods that can serve as surrogates for clinical performance and as Quality by Design and risk management tools.[7]

Case Study: Dissolution-Driven Development of Methylphenidate Extended-Release Products

Extended-release methylphenidate formulations for ADHD provide a classic example of dissolution-driven development. Products such as Metadate CD, Concerta, and other modified-release formulations rely on carefully engineered release profiles to achieve therapeutic benefit.

For these systems, dissolution testing was not merely confirmatory—it was foundational. Biphasic and ascending release profiles required dissolution methods capable of resolving early and late-stage release behavior, and regulatory approval relied heavily on dissolution-based comparisons, often using partial AUCs rather than traditional single-point metrics.

These products illustrate how dissolution science evolved alongside formulation complexity, reinforcing its central role in modern drug development.

Case Study: Dissolution Behavior of Amorphous Solid Dispersions

Amorphous solid dispersions (ASDs) remain one of the most effective strategies for improving the apparent solubility of poorly soluble drugs. However, their performance is governed by complex, dynamic processes that are only revealed through dissolution testing.

The well-known spring-and-parachute concept describes the rapid generation of supersaturation followed by polymer-mediated stabilization. More recently, additional phenomena—such as liquid–liquid phase separation (LLPS), amorphous–amorphous phase separation, and the limit of congruence (LoC)—have been shown to critically influence dissolution behavior and achievable drug loading during this process. When drug and polymer no longer dissolve congruently, or when drug-rich phases formed during dissolution evolve into solid phases that impede release, a dramatic loss of dissolution performance can occur, often described as “falling off the cliff.” Dissolution testing is the primary experimental tool for identifying this boundary and for optimizing formulation composition and drug loading. Improved Pharma’s automated dissolution capabilities, combined with deep expertise in amorphous systems, make it an ideal partner for ASD screening, optimization, and risk reduction—allowing higher-performing formulations to advance with greater confidence.

Conclusion

Since its adoption by the United States Pharmacopeia (USP) in the 1970s, dissolution testing has proven to be one of the most powerful tools for understanding and controlling drug product performance. It can be both a diagnostic and predictive tool, providing insight into a product’s materials science, formulation design, and manufacturing history. When used strategically, it reduces risk, accelerates development, and aligns scientific understanding with regulatory expectations.

Improved Pharma’s expanded automated dissolution capabilities build directly on this foundation, providing clients with high-quality, decision-enabling data that support faster, higher-quality development pathways.

  1. Dressman, J.B., et al., Dissolution testing as a prognostic tool for oral drug absorption: immediate release dosage forms. Pharmaceutical research, 1998. 15(1): p. 11-22.
  2. Byrn, S.R., Solid state chemistry of drugs. 1982: Academic Press.
  3. Byrn, S.R., Pfeiffer, R.R., Stowell, J.G., Solid State Chemistry of Drugs. 1999: SSCI, Inc.
  4. Byrn, S.R., G. Zografi, and X.S. Chen, Solid-state properties of pharmaceutical materials. 2017: John Wiley & Sons.
  5. Byrn, S.R., G. Zografi, and X.S. Chen, Solid-State Materials in Pharmaceutical Chemistry: Properties, Characterization, and Applications. 2025: John Wiley & Sons.
  6. Taylor, L.S. and G. Zografi, From Unwanted Annoyances to Oral Delivery Saviors: The Rollercoaster Journey of Amorphous Drugs. Molecular Pharmaceutics, 2025.
  7. Abend, A., et al., Dissolution testing in drug product development: workshop summary report. The AAPS Journal, 2019. 21(2): p. 21.