Formulation Screening for pH Modification in Solid Dosage Forms

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1. 

   PREreview

   Jul 10, 2026

   This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/21297367.

   Does the introduction explain the objective of the research presented in the preprint? Yes The introduction clearly establishes the research objective by first defining the problem: weakly basic APIs have poor solubility at elevated gastric pH, which limits their bioavailability in patients with achlorhydria. It then reviews existing strategies and their drawbacks, identifies a research gap regarding the optimal way to incorporate a pH-modifier, and explicitly states the aim of evaluating different formulation approaches with fumaric acid to enhance bioavailability while ensuring …

   This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/21297367.

   Does the introduction explain the objective of the research presented in the preprint? Yes The introduction clearly establishes the research objective by first defining the problem: weakly basic APIs have poor solubility at elevated gastric pH, which limits their bioavailability in patients with achlorhydria. It then reviews existing strategies and their drawbacks, identifies a research gap regarding the optimal way to incorporate a pH-modifier, and explicitly states the aim of evaluating different formulation approaches with fumaric acid to enhance bioavailability while ensuring manufacturability and patient-centricity. Finally, it provides context by referencing a previous proof-of-concept study in dogs and outlines the methodological approach using biorelevant dissolution tests to screen ten formulation prototypes.

   Are the methods well-suited for this research? Highly appropriate The methods are highly appropriate because they employ a systematic design of ten formulation prototypes with controlled variables, use physiologically relevant two-stage dissolution testing in three distinct biorelevant media (healthy, low-buffered, and high-buffered achlorhydric conditions) to comprehensively evaluate bio-performance, and incorporate additional assessments of stability under accelerated conditions and patient-centricity factors such as pill burden and swallowability. All manufacturing processes were rigorously controlled, dissolution tests were performed on six replicates with statistical reporting, and the authors provided clear justifications for each methodological choice while acknowledging the limitations of in vitro testing. This combination of systematic formulation design, biorelevant testing conditions, multiple evaluation criteria, and transparent execution provides a robust and reliable foundation for drawing valid conclusions about the optimal formulation strategy.

   Are the conclusions supported by the data? Highly supported The conclusions are highly supported because they are directly derived from the experimental dissolution data, which clearly identified the over-encapsulated tablet as the most robust formulation in the highly discriminative buffered achlorhydric medium, while acknowledging that other prototypes performed adequately only under less challenging conditions. The authors honestly recognize the limitations of in vitro testing, explicitly stating that in vivo confirmation is needed, and they integrate findings from stability studies and patient-centricity assessments to provide a balanced and practical recommendation. Overall, the conclusions are data-driven, cautious, and do not overreach beyond what the evidence supports, making them thoroughly justified and realistic.

   Are the data presentations, including visualizations, well-suited to represent the data? Somewhat appropriate and clear Overall, the visualizations are adequate for conveying the key patterns and conclusions, and a reader can follow the results without major difficulty. However, improvements in accessibility, labeling, statistical annotation, and inclusion of all prototypes would make them highly effective.

   How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Very clearly The discussion is very clear because the authors systematically explain their findings, acknowledge in vitro limitations, and propose practical next steps. They provide mechanistic reasons for prototype performance, honestly note that in vivo confirmation is needed, and integrate stability and patient-centricity factors into their conclusions. Their balanced interpretation and concrete recommendations for future research make the discussion exceptionally thorough and insightful.

   Is the preprint likely to advance academic knowledge? Highly likely These contributions are likely to influence both academic research and industrial practice in the development of oral solid dosage forms for weakly basic drugs.

   Would it benefit from language editing? No The preprint is written in clear, professional, and technically precise English. The language is consistent with standard scientific writing in pharmaceutical sciences. Any minor stylistic imperfections (e.g., occasional wordiness or minor punctuation variations) do not hinder comprehension or detract from the scientific content. The authors clearly communicate their objectives, methods, results, and conclusions without ambiguity. Therefore, the preprint would not significantly benefit from language editing, though minor polishing could be applied for stylistic improvement.

   Would you recommend this preprint to others? Yes, it's of high quality While minor language polishing could be applied, the preprint is technically sound, methodologically robust, and offers significant insights that would be valuable to researchers in pharmaceutical sciences, biopharmaceutics, and formulation development.

   Is it ready for attention from an editor, publisher or broader audience? Yes, after minor changes These are minor revisions that do not affect the scientific validity or significance of the work. Once addressed, the preprint would be ready for journal submission and broader dissemination.

   Competing interests

   The author declares that they have no competing interests.

   Use of Artificial Intelligence (AI)

   The author declares that they used generative AI to come up with new ideas for their review.

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2. Version published to 10.20944/preprints202605.1892.v1

   May 27, 2026