WHEN ORAL SUSPENSIONS ARE THE ONLY CHOICE

Oral administration is the most common route of delivery for many therapeutic agents due to its convenience, ease of use, and non-invasiveness.¹ Liquid dosage forms are often the ideal solu­tion to accommodate diverse patient groups such as pediatrics, geriatrics, and up to 16% of the general population with dyspha­gia.² Swallowing difficulties are also prevalent in patients with dis­orders resulting from various conditions like stroke or neurological diseases. In severe cases, these conditions may re­quire enteral feeding via nasogastric (NG) or percutaneous en­doscopic gastrostomy (PEG) tubes. In these settings, an oral suspension is not just a matter of preference but often the only viable means of ensuring that patients continue to receive their medications safely and consistently.

With nearly 90% of drug entities being poorly water-soluble, addressing solubility and bioavailability is a critical priority in drug development.³ Dispersing the drug is one of the most direct ap­proaches to dealing with a poorly soluble active pharmaceutical ingredient (API). However, this creates a new set of complex chal­lenges. A successful suspension demands careful consideration of chemical and physical stability, palatability for oral adminis­tration, accurate and flexible dosing, and precise in-vitro dissolu­tion. Viscosity especially plays a vital role for patients requiring enteral feeding, as it directly impacts both administration and drug delivery.

This article introduces a new approach to perfecting oral sus­pension formulation. It is centered on the strategic use of a “novel” synthetic functional excipient, magnesium aluminometasilicate (MAS). We explore its unique properties, its suc­cessful journey through the FDA approval process, and its appli­cation in a real-world case study on NSAIDs. By showcasing how we successfully navigated the challenges of working with a novel excipient and a complex suspension system, we aim to provide formulators with a clear pathway to overcome their most difficult challenges and drive innovation in drug development. Ultimately, our work illustrates how the deliberate choice of excipients can transform an otherwise limited formulation into a patient-friendly product with commercial longevity.

WHY MAGNESIUM ALUMINOMETASILICATE?

MAS possesses unique functional properties that were essen­tial for the success of our oral suspension development. Its high surface area and porous structure enable controlled dissolution rate, API dispersion, and amorphous stabilization, while its chem­ical composition provides additional benefits for stability and its potential to indirectly contribute to taste masking. These proper­ties directly address the most common challenges encountered when moving from early formulation screening to late-stage de­velopment.

Their impact will be further detailed in our case study, which highlights how MAS was successfully incorporated into our FDA approved oral suspension product. The decision to include this novel material in our formulation was driven by its functional ad­vantages, despite the complexity of the regulatory pathway. This approved product supports our formulation science and regulatory strategy to achieve a new standard in oral suspension delivery.

THE CHALLENGE & OPPORTUNITY OF A NOVEL EXCIPIENT

In the eyes of the FDA, an excipient is considered “novel” when it has not been previously used in an approved drug prod­uct in the U.S. for the intended route and dosage level.⁴ A novel excipient often dif­fers significantly from established excipi­ents, which are typically natural or semi-synthetic. MAS fits this definition be­cause it is a synthetic compound, unlike its counterpart, Magnesium Aluminum Sili­cate, which is naturally derived from puri­fied smectite clays.⁵

The novelty of MAS and other syn­thetic materials can create confusion in the public domain. For instance, there are often confounding CAS numbers and mis­leading descriptions of natural and syn­thetic materials as equivalent. This lack of clarity and the absence of a defined regu­latory pathway for such materials high­lights the need for a rigorous strategy. While synthetic materials like MAS are often valued for their high purity and lot-to-lot consistency, they come with high reg­ulatory barriers, which often discourage pharmaceutical companies from using ex­cipients beyond those already approved. As a result, the adoption of novel excipi­ents lags significantly behind scientific dis­covery, creating a gap between what is technically possible and what is practically implemented in commercial products.

Securing approval for a novel excipi­ent is a rigorous and data-intensive process. Novel excipients are not listed on the FDA’s Inactive Ingredient Database (IID), so their safety and performance must be thoroughly demonstrated through for­mal regulatory submissions. Our team successfully navigated this pathway by collaborating closely with the manufac­turer/supplier of MAS, who submitted a detailed Drug Master File (DMF) to the FDA. We provided expert input and con­ducted a thorough review of the open por­tion of the DMF, which contained comprehensive data on chemistry, manu­facturing, and controls. An extensive toxi­cological evaluation and the full toxicokinetic behavior of other MAS grades and related compounds were also pre­sented to justify the safety and effectiveness of this excipient, leading to a positive out­come and regulatory acceptance of the material. The FDA’s formal acknowledg­ment of MAS’s approvability was a key milestone, demonstrating our expertise in managing complex regulatory processes and our ability to incorporate novel mate­rials into new drug formulations.

A CASE STUDY: FORMULATING AN NSAID SUSPENSION

The Core Roles of MAS
The unique challenges of formulating select NSAIDs, which are known for their poor solubility and bitter taste, provide a compelling use case for a novel excipient like MAS. Its high surface area (300 m3/gm) and porous structure facilitate the adsorption of the API at a near-molecular level, which enhances dispersion and pre­vents particle aggregation, thereby maxi­mizing the drug’s exposure to gastrointestinal fluids and leading to a more consistent dissolution profile. Fur­thermore, MAS helps stabilize the amorphous form of the drug, preventing recrys­tallization and maintaining the controlled dissolution properties. For these NSAIDs, this stabilization can be the difference be­tween a formulation that delivers a consis­tent and reproducible release profile and one that fails to achieve reliable results.

Beyond its impact on drug perform­ance, MAS contributes significantly to product stability and patient acceptability. A key quality attribute of elegant suspen­sions is redispersibility: the ability to be easily and homogeneously re-dispersed with gentle shaking after sedimentation. The highly porous nature of MAS slows settling and caking of suspended drug particles, ensuring dose uniformity throughout the product’s shelf-life. Its abil­ity to effectively encapsulate drug particles and promoting fine, uniform dispersion, also indirectly contributes to taste masking. This barrier formation can shield direct contact with taste receptors in the mouth, and the improved drug dispersion can prevent localized high concentrations of bitter drug in the suspension and poten­tially help reduce the need for extensive flavor work. In pediatric populations espe­cially, palatability is often the single largest driver of adherence, and the potential for MAS to help minimize bitterness offers a practical route to better compliance with­out relying solely on flavoring agents or sweeteners.

Achieving an Elegant Suspension: Synergistic Excipients
By combining MAS with other care­fully selected functional excipients, we op­timized the in-vitro dissolution profile while improving overall patient experience. For example, xanthan gum (XG), a key rheology modifier, was crucial for providing long-term physical stability. When dis­persed in an aqueous solution, XG forms a structured network that effectively holds drug particles in place, preventing sedi­mentation or caking. Its pseudoplastic be­havior ensures the suspension exhibits high viscosity at rest. When subjected to shear force like shaking, pouring, or swal­lowing, its viscosity temporarily decreases, allowing for easy handling and adminis­tration.⁶ This is a critical property for pa­tients requiring enteral feeding, as the shear-thinning behavior allows smooth administration through a narrow tube while the high viscosity at rest prevents set­tling within the bottle. The rheological con­trol also enhances swallowability and mouthfeel by providing a smooth, consis­tent texture and preventing grittiness, which is particularly beneficial for patients with dysphagia.

Our formulation strategy incorpo­rated additional excipients to further refine the suspension system. Glycerin acts as humectant, co-solvent, and stabilizing agent to prevent the formulation from dry­ing out and impacting redispersibility. The system also includes tight pH control, which is essential for product quality, shelf life, and patient acceptability. In certain it­erations, we also explored the strategic use of an ion exchange resin to further en­hance taste masking capabilities, particu­larly for actives with more pronounced bitter taste. The result is a formulation that proficiently solved the challenge of bitter­ness and improved chemesthetic proper­ties, such as throat catch or burning sensation associated with select poorly sol­uble NSAIDs.

This carefully balanced combination of MAS with rheology modifiers, humec­tants, and taste masking agents demonstrates our expertise in developing elegant and effective oral suspensions. Our inno­vative suspension system delivers im­proved dose uniformity, long-term physical stability, precise in-vitro dissolution, and better mouthfeel and swallowability, all of which contribute to superior patient com­pliance.

Beyond elevating overall product quality, it creates a visually appealing, dye-free formulation. Visual aspects should not be underestimated — patients often asso­ciate clarity, color, and consistency with product quality, and a suspension that looks elegant can inspire greater trust and acceptance.Overall, a comprehensive formula­tion approach reflects the reality that no single excipient, however novel, can solve every challenge. Success depends on un­derstanding the interactions of multiple components working in sync.

A PATHWAY FOR FORMULATION EXCELLENCE

The successful journey from a novel excipient to an FDA-approved product is a compelling testament to the blend of ex­pert formulation science and regulatory understanding. This case study demon­strates that excipients like MAS are power­ful tools, but their full potential is unlocked through the strategic use of a complete ex­cipient system. By successfully leveraging magnesium aluminometasilicate’s unique capabilities, this approach has shown that it is possible to create innovative, patient-centric suspensions that are both thera­peutically effective and commercially viable. This experience highlights the criti­cal role of expert formulation in a complex environment and offers a pathway for formulators seeking to accelerate their prod­uct development with new materials and methodologies.

REFERENCES 

1. Alqahtani, M.S., Kazi, M., Alsenaidy, M.A., et al. Advances in Oral Drug Delivery. Front Pharmacol. 2021 Feb 19;12:618411. doi: 10.3389/fphar.2021.618411. PMID: 33679401; PMCID: PMC7933596.
2. Mittal, R.K., Zifan, A. Why so Many Patients With Dysphagia Have Nor­mal Esophageal Function Testing. Gastro Hep Adv. 2024;3(1):109-121. doi: 10.1016/j.gastha.2023.08.021. Epub 2023 Oct 5. PMID: 38420259; PMCID: PMC10899865.
3. Xie, B., Liu, Y., Li, X., et al. Solubilization techniques used for poorly water-soluble drugs. Acta Pharm Sin B. 2024;11:4683-4716. doi:10.1016/j.apsb.2024.08.027.
4. U.S. Pharmacopeia. Quality Matters. Novel Excipients: New Hope for Therapeutic Innovations. Accessed August 7, 2025. https://qualitymat­ters.usp.org/novel-excipients-new-hope-therapeutic-innovations.
5. Vanderbilt Minerals, LLC. VEEGUM® EZ Magnesium Aluminum Silicate. Accessed August 14, 2025. https://www.vanderbiltminerals.com/prod­ucts/veegum-ez/rx-veegum-magnesium-aluminum-silicate.
6. Layek, B. A Comprehensive Review of Xanthan Gum-Based Oral Drug Delivery Systems. Int J Mol Sci. 2024;25(18):10143. doi:10.3390/ijms251810143.

Mary Schuster earned her degree in biochemistry from the Georgia Institute of Technology in Atlanta, GA, and has built a career spanning nutraceuticals, molecular biology, and pharmaceuticals. She began her journey in the pharmaceutical industry as a scientist at Kiel Laboratories, where she gained hands-on experience in drug formulation and analytical method development. This foundational experience gave her a deep understanding of pharmaceutical operations and laid the groundwork for her current role as a Business and Innovation Strategist, where she bridges the gap between innovation and market-ready solutions.