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Post-Marketing Quality Evaluation and in Vitro Dissolution Kinetics of Multi-Source Diclofenac Potassium 50 Mg Tablets Marketed in Sudan: Implications for Therapeutic Interchangeability

While five commercial diclofenac potassium 50 mg tablet brands marketed in Sudan met basic pharmacopeial quality standards, advanced dissolution profiling and kinetic modeling revealed significant release profile differences between local and imported generics, highlighting the need for such methods in post-marketing surveillance to ensure therapeutic interchangeability.

Original authors: Orwa Siddig, Ahmed O. Alnajjar, Abdalla A Elbashir, Rami Ahmed

Published 2026-08-31

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CC BY 4.0

Original authors: Orwa Siddig, Ahmed O. Alnajjar, Abdalla A Elbashir, Rami Ahmed

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

Pain relief is a universal human need, and for decades, doctors have relied on a specific class of medicines to treat inflammation and discomfort. Among these, a drug called diclofenac potassium is a common choice for immediate relief. Unlike some versions of the drug that take time to work, this salt form is designed to dissolve quickly in the body, allowing the medicine to enter the bloodstream and start working within minutes. Because this drug is essential, it is manufactured by many different companies around the world. While the original version is made by the company that first discovered it, other companies produce generic copies that contain the exact same active ingredient. For these copies to be safe and effective replacements, they must not only contain the right amount of medicine but also release that medicine into the body at the same speed as the original. If a generic pill dissolves too slowly, a patient might wait too long for pain relief; if it dissolves too fast, it could cause irritation or other issues. Ensuring that these different versions perform identically is a critical task for health regulators, especially in regions where medicines travel through hot and humid conditions that can sometimes alter their quality.

In Sudan, where the climate can be harsh on stored medicines, researchers set out to examine the quality of five different brands of diclofenac potassium tablets available in local pharmacies. The team, working from universities in Sudan and Saudi Arabia, gathered samples of the original brand and four generic versions, including two made locally and two imported from other countries. They did not test these pills on people, but instead put them through a rigorous series of laboratory checks designed to mimic what happens inside the human body. First, they inspected the physical appearance of the tablets, checking their size, shape, and color to ensure they were uniform. They weighed each tablet individually to confirm they were all the same mass, and they tested how hard they were by measuring the force required to crush them. They also checked how easily the tablets crumbled under friction and how quickly they broke apart in water, which is the first step before the medicine can dissolve. Finally, they measured the actual amount of active drug inside each pill to ensure it matched the label.

The initial physical tests showed that all five brands were well-made. Every tablet met the standard requirements for weight, hardness, and how quickly it fell apart in water. The amount of active drug in each brand was also correct, falling within the safe range expected for a 50-milligram dose. At this stage, a standard check might have declared all five products as identical and safe to use interchangeably. However, the researchers went a step further by watching how the drugs dissolved over time. Instead of just checking if the drug was gone after a set time, they measured how much medicine had dissolved at five, ten, fifteen, thirty, forty-five, and sixty minutes. This detailed timeline revealed that while the pills looked the same on the outside, they behaved very differently once they started to break down.

The imported generic brands performed very similarly to the original drug, releasing their contents at a steady, predictable pace that matched the reference product. However, the two locally manufactured brands showed significant deviations. One local brand released its medicine much faster than the others, dumping nearly three-quarters of its dose within the first ten minutes. This rapid release could potentially lead to a sudden spike in the drug's concentration in the body, which might increase the risk of stomach irritation for some patients. The other local brand behaved in the opposite way; it dissolved too slowly. While it eventually released most of its drug, it failed to meet the requirement of releasing at least 80 percent of the dose within thirty minutes, delivering only about 76 percent by that time. This delay could mean that a patient taking this specific brand might wait longer than necessary for their pain to subside.

The study highlights a crucial gap in how medicines are sometimes evaluated. Standard tests often look at a single point in time to see if a drug has dissolved enough, but this approach can miss important differences in how the drug is released. By using a more detailed timeline and comparing the entire shape of the release curve, the researchers found that two of the local brands, despite passing the basic quality checks, were not truly equivalent to the original in how they delivered their medicine. The findings suggest that for immediate-release drugs like diclofenac potassium, where speed matters, regulators should consider using these more detailed dissolution profiles to decide whether different brands can be safely swapped for one another. While the study did not test how these differences affected patients directly, the laboratory results provide a strong warning that not all generic versions of the same drug perform the same way, and closer monitoring could help ensure that patients receive consistent and reliable pain relief.

Technical Summary: Post-Marketing Quality Evaluation of Diclofenac Potassium Tablets in Sudan

Problem Statement
The expansion of multi-source generic medicines has improved access to essential drugs in low- and middle-income countries like Sudan. However, therapeutic interchangeability relies not only on the presence of the same active pharmaceutical ingredient (API) but also on consistent pharmaceutical quality and comparable in vitro performance. While immediate-release formulations like diclofenac potassium require rapid dissolution for prompt analgesic action, variations in formulation, manufacturing processes, or storage conditions (particularly under tropical climates with elevated temperatures and humidity) can alter dissolution profiles. Existing literature indicates a gap in the systematic comparison of dissolution profiles and release kinetics for diclofenac potassium tablets in African markets. Furthermore, routine post-marketing surveillance often relies on single-point dissolution testing, which may fail to detect clinically relevant differences in release behavior between generic and innovator products.

Methodology
This comparative cross-sectional laboratory study evaluated five commercially available brands of immediate-release diclofenac potassium 50 mg tablets marketed in Khartoum, Sudan. The sample set included one innovator product (Brand A, Switzerland) and four generic brands (Brands B–E; two locally manufactured and two imported from Jordan and Egypt). Sampling was purposive, selecting the most frequently dispensed brands from community pharmacies and government hospitals, with five independent market samples collected per brand.

The evaluation followed United States Pharmacopeia (USP 44–NF 39) specifications and included:

Physicochemical Characterization: Visual inspection, tablet dimensions, weight uniformity, mechanical breaking force (hardness), friability, and disintegration time.
Chemical Assay: Quantification of API content using High-Performance Liquid Chromatography (HPLC) with a C18 column and photodiode array detection.
In Vitro Dissolution Profiling: Multi-point dissolution testing (0, 10, 20, 30, 45, and 60 minutes) in pH 6.8 phosphate buffer at 37°C using the USP Apparatus II (paddle method).
Data Analysis: Dissolution profiles were analyzed using Dissolution Efficiency (DE₃₀), the model-independent similarity factor ( $f_2$ ), and mathematical kinetic modeling (Zero-order, First-order, Higuchi, Hixson–Crowell, Korsmeyer–Peppas, and Weibull models) using DDSolver software. Statistical significance was determined via one-way ANOVA with Tukey's post hoc test ( $p < 0.05$ ).

Key Results

Physicochemical Quality: All five brands complied with USP specifications for weight variation, hardness, friability, disintegration time, and assay (90.0–110.0% of labeled claim). No visual defects or batch-to-batch variations were observed.
Dissolution Performance: Single-point testing at 30 minutes revealed that four brands met the requirement of $\ge$ 80% drug release. However, Brand E (local) failed this criterion, releasing only $76.6 \pm 1.4\%$ .
Profile Similarity ( $f_2$ ): Multi-point profile comparison showed significant divergence:
- Brands B and C (imported generics) demonstrated similarity to the innovator ( $f_2 = 53.4$ and $86.7$, respectively).
- Brand D (local) and Brand E (local) exhibited dissimilar profiles ( $f_2 = 42.1$ and $46.3$, respectively).
- Brand D displayed an excessively rapid release (approx. 75% in 10 min), while Brand E showed a delayed release compared to the innovator.
Kinetic Modeling: All brands followed first-order release kinetics ( $R^2 > 0.99$ ). Weibull shape parameters confirmed formulation-dependent differences; Brand D had a shape parameter ( $\beta$ ) of 1.46 (indicating rapid release), while Brand E had a $\beta$ of 1.05 (diffusion-controlled).

Key Contributions
The study provides the first systematic post-marketing evaluation of diclofenac potassium tablets in Sudan, demonstrating that:

Routine single-point dissolution testing is insufficient to detect formulation-related differences in drug release behavior among generic products.
Multi-point dissolution profiling, combined with $f_2$ similarity factor analysis and kinetic modeling, can identify clinically relevant deviations (such as dose-dumping risks or delayed onset) even when products pass standard compendial assays.
Local manufacturing variations in Sudan may lead to significant differences in release kinetics compared to innovator and imported generic products, despite meeting basic physical quality standards.

Significance and Claims
The authors claim that while all evaluated brands met basic pharmacopeial quality standards, the observed differences in release behavior highlight the limitations of relying solely on routine single-point testing for post-marketing surveillance. The paper asserts that incorporating multi-point dissolution profile comparison, dissolution efficiency analysis, and kinetic modeling into regulatory frameworks would strengthen decisions regarding generic substitution and therapeutic interchangeability.

The study concludes that these advanced analytical approaches offer independent evidence of product quality and can assist regulatory authorities, such as the Sudanese National Medicines and Poisons Board (NMPB), in ensuring the consistent quality of multi-source generic medicines. The authors explicitly note that while the findings suggest potential differences in therapeutic performance, the study is limited to in vitro evaluation and does not provide direct evidence of in vivo bioequivalence or clinical efficacy differences.

Technical Summary: Post-Marketing Quality Evaluation of Diclofenac Potassium Tablets in Sudan

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