Usha Chowdhury is Technical Services Manager, Health and Nutrition, at Univar Solutions.

Usha Chowdhury 

Green gelatin capsule resting on a translucent amber liquid drop, isolated on transparent background | Image Credit: ©Nina -stock.adobe.com

As consumer demand continues to grow for convenient, high-performance health and wellness products, innovative delivery technologies are becoming increasingly important in supplement formulation. Dual-delivery capsule systems offer a sophisticated approach to nutrient administration by enabling the immediate and targeted release of active ingredients within a single dosage form. By protecting sensitive probiotics,

 optimizing ingredient performance, and reducing the need for multiple products, this technology enhances efficacy, improves consumer compliance, and creates new opportunities for differentiated, multi-benefit formulations.

A dual-delivery capsule platform technology was designed and evaluated for next-generation pharmaceutical and nutraceutical products. The platform enables the delivery of multiple APIs within a single dosage unit, reducing pill burden and simplifying dosing regimens to enhance patient convenience, compliance, and overall user experience.

The dual-capsule design provides formulation flexibility by combining liquid and solid fills or immediate-release and sustained-release ingredients within 1 system. This approach allows for the physical separation of sensitive or potentially incompatible actives, helping to preserve stability, efficacy, and product quality throughout the product lifecycle.

Dual-capsule technology offers a significant innovation advantage over traditional capsules by enabling multi-benefit formulations, ingredient protection, targeted release, and premium consumer appeal, making it particularly attractive for advanced nutraceutical products in gut health, women's wellness, sports nutrition, cognitive health, and beauty-from-within categories

Dual-capsule technology provided significantly greater protection of acid-sensitive digestive enzymes and resulted in substantially higher enzyme activity in the upper small intestine compared with standard immediate-release capsules.

As part of the development program, hypromellose (HPMC) and gelatin capsules were evaluated for their suitability in dual delivery applications. Assessments included compatibility with liquid and solid formulations, manufacturing feasibility, stability, capsule performance, and overall functionality to identify the optimal platform for future combination product development

Researchers designed 2 capsule-in-capsule configurations and evaluated the dissolution profile of ginger (Gingeren, Ennature Biopharma) granules independently for use as a sustained-release ingredient with turmeric oil and coenzyme Q10 (COQ10) oils as liquid dosage forms.

The dual capsule configurations were as follows:


Inner capsule: Size 3 capsule - liquid
Outer capsule: Size 0 capsule – Solid Ginger granules.


Inner capsule: Size 3 capsule - Solid Ginger granules.
Outer capsule: Size 0 capsule – liquid

. The researchers manufactured an R&D-scale batch of 100 dual delivery capsules was manufactured for each design configuration. Liquid formulations (200 µL) were accurately dispensed into the designated capsules using a calibrated analytical pipette to ensure precise fill volumes and reproducible dosing. Sustained-release ginger granules (100 mg) were individually weighed and filled into the appropriate capsule compartment.

Assembly of the dual capsule system was performed using a capsule filling system (ProFiller 1000, Torpac). The outer capsule was first filled with the designated formulation, followed by insertion of the prefilled inner capsule. The assembled unit was then closed to produce the final capsule configuration.

For designs utilizing an outer capsule containing a liquid formulation, capsule integrity was enhanced through the application of a proprietary HPMC-based banding solution.The solution was applied to the capsule-locking region to provide an effective seal, reduce the risk of leakage in storage and transportation.

Researchers evaluated10 filled capsules of each design for fill weight uniformity to verify dosing accuracy and process consistency using 

 Disintegration performance of the assembled dual-capsule systems was evaluated using a disintegration tester (Sotax) per 

Dissolution testing was performed using a USP dissolution test apparatus (Lab India)in accordance with USP guidelines 

 at designed time points. High-performance liquid chromatography (HPLC) conditions were as follows:

Different retention times were recorded for actives Gingerol and Shogaols.

Visual inspection demonstrated that filled capsules from both dual-capsule configurations maintained excellent physical integrity and uniform appearance. Researchers observed no leakage, deformation, or shell defects throughout the study.

The applied banding solution effectively sealed the capsule junction, preventing liquid migration and ensuring containment of the liquid-filled compartment. These results confirm the suitability of the banding process for maintaining product quality, capsule integrity, and formulation stability within the dual-capsule system (see 

Figure 1: Visual Testing for Final Capsules (Figure courtesy of the authors)

Fill-weight measurements were performed in accordance with General Chapter <905>

requirements. All tested dual-capsule units complied with the established ±5% specification, demonstrating acceptable weight variation and uniformity. The results indicate that both capsule designs can be filled reproducibly, with consistent dosage delivery and adequate process control. This level of fill weight consistency supports the manufacturability and scalability of the dual-capsule system (see 

Figure 2: Weight Variation Testing Analysis (Figure courtesy of the authors)

. Researchers performed disintegration testing in accordance with USP requirements for filled capsules. Both dual-capsule configurations exhibited complete disintegration within 30 minutes per USP specifications. The results indicate that the dual-capsule architecture did not hinder capsule shell hydration, rupture, or release of the encapsulated contents. Furthermore, the rapid and consistent disintegration observed across both designs demonstrates the suitability of the system for multi-compartment oral delivery while maintaining compendial performance standards (see 

Figure 3: Disintegration Profile Analysis (Figure courtesy of the authors)

Dissolution testing confirmed successful release of Ginger granules at the specified time intervals. Results support the feasibility of incorporating granule formulations within the dual-capsule delivery platform while maintaining the intended release profile (see 

Figure 4: Dissolution Testing Profile for Ginger Granules (Figure courtesy of the authors)

The results of this study demonstrate that the dual-capsule delivery system is a robust, scalable, and versatile oral delivery platform capable of successfully incorporating multiple dosage forms within a single unit while maintaining acceptable performance characteristics. Complete disintegration within 30 minutes confirmed the effective release of both capsule compartments, demonstrating that liquid and solid formulations can be combined within a single dosage form without compromising functionality or release performance.

Among the capsule materials evaluated, HPMC capsules provided more consistent disintegration behavior, improved structural integrity, and greater reliability within the dual-capsule configuration compared with gelatin capsules. These attributes support the suitability of HPMC capsules for advanced multi-compartment delivery applications where formulation stability and reproducible performance are critical.

Overall, the study confirms that dual-capsule technology is a practical, manufacturable, and automation-compatible platform for delivering multiple dosage forms within a single unit. The system has potential pharmaceutical and nutraceutical applications by enabling the separation and targeted delivery of incompatible ingredients, acid-sensitive compounds, oxidation-prone actives, poorly soluble APIs, probiotics, enzymes, oils, and botanical extracts. The platform enhances formulation flexibility, product stability, patient convenience, and opportunities for the development of next-generation combination products.

The primary regulatory focus for dual capsule supplements is demonstrating product quality, stability, ingredient compatibility, manufacturing control, and substantiation of any release-profile or bioavailability claims. While dual capsule products are regulated as dietary supplements under the same framework as conventional capsules, their more complex design requires additional scientific and quality documentation to support product performance and shelf-life claims.

 Although the dual-capsule system demonstrated successful incorporation of liquid and solid dosage forms with acceptable disintegration performance, further studies are required to assess long-term stability, dissolution characteristics, inter-compartment compatibility, moisture migration, and large-scale manufacturing robustness. In addition, the increased capsule size and manufacturing complexity may present challenges for certain applications and require optimization for commercial implementation.

These limitations do not diminish the platform's value; rather, they identify key development areas necessary to advance dual-capsule technology toward commercial pharmaceutical and nutraceutical products.

Bron PA, Catalayud, M, Marzorati M, Pane M, Kartal E, Dhir R, Reid G. Delivery of metabolically neuroactive probiotics to the human gut. 

International Journal of Molecular Sciences

Azari E K, Govaert M, Duysburgh C, Glab S, Marzorati M, Saiyed Z. Evaluation of targeted-release capsule formulations for protection of the acid-sensitive enzyme pancreatin under fasted and fed intestinal conditions in vitro. 

Erin Burke, PhD, is North America technical director for Solution Centers at Univar Solutions. She leads technical teams responsible for formulation development, innovation, customer collaboration, and application testing across multiple market segments. Dr. Burke works closely with suppliers and customers to accelerate commercialization of new ingredient technologies and develop market-relevant solutions that address evolving industry and consumer needs.

Usha Chowdhury is the pharma technical services manager at Univar Solutions' Houston Solution Center, leading pharmaceutical and nutraceutical formulation innovation in health, wellness, and nutrition. With over 25 years of experience across academia, biotechnology, pharmaceuticals, and nutraceuticals, she has held scientific leadership roles at Thermo Fisher Scientific, Reckitt, and Texas A&M University College of Medicine. Under her leadership, innovation projects from the Houston Solution Center have been presented at leading industry conferences, including AAPS and Excipient World, demonstrating the team's commitment to advancing formulation science and customer-focused innovation.

Jyothi Gautam is senior manager technical sales and works closely with distributors, brand owners and manufacturers and is responsible for providing technical, regulatory and commercial support.

Articles

Dual-delivery capsule-in-capsule systems enable co-formulation of liquid and solid, immediate- and sustained-release actives within a single oral unit, improving convenience and allowing physical separation of sensitive or incompatible ingredients. Two configurations combining sustained-release ginger granules with turmeric oil and coenzyme Q10 were manufactured and tested under USP methods. Both designs demonstrated intact appearance, acceptable weight uniformity (±5%), full disintegration within 30 minutes, and appropriate dissolution of ginger actives. HPMC shells outperformed gelatin for disintegration consistency and structural reliability.

A dual delivery capsule platform provides delivery of multiple APIs with a single dosage unit, which reduces pill burden and simplifies dosing regimens.

A Capsule-in-Capsule Platform for Multi-Phase Release of Liquid and Solid Formulations

Fast dissolving oral film, a solid dosage form which disintegrate and dissolve within one minute when placed in the mouth without drinking water or chewing, fast soluble films are thin and act rapidly | Image Source: ©Tamer -stock.adobe.com

As consumer expectations evolve and the demand for more patient-friendly medication formats grows, innovation in drug delivery systems has become essential. Orally dissolving films (ODFs) have emerged as a solution, particularly for individuals experiencing pill fatigue or those who struggle with swallowing such as children, the elderly, or patients with dysphagia

ODFs are ultra-thin, flexible strips that dissolve quickly when placed on the tongue, requiring no water. They are designed to deliver active ingredients, whether pharmaceutical or nutritional, directly through the oral mucosa, offering a fast and efficient route into the bloodstream. While examples of ODFs containing nutraceutical and pharmaceutical active ingredients exist in the marketplace today, most of them contain just 1 or 2 active ingredients set in a polysaccharide-based matrix film.

The aim of this study was to develop and optimize an ODF formulation containing a synergistic blend of active ingredients that support energy and mental alertness in a strategic combination of natural and synthetic excipients to achieve a balance between controlled actives release and rapid onset of action.

A series of formulations were developed using the solvent casting technique that allow the adjustment of polymer concentration, solvent type, and drying conditions and suitable for heat-sensitive vitamins as the drying temperatures are generally lower. The optimized formulation included synthetic polymer hydroxypropyl methylcellulose (HPMC) (Headcel 60HD4000) (2%), natural polymer high methoxyl rapid set pectin (10%), polyethylene glycol (PEG) (1%), lactose monohydrate (2%), and sodium starch glycolate (1%).

Active ingredients and flavors included the following:

Delivering of dosages (100% DV) based on 200mg ODF

sour cherry was used as the flavoring agent, and vitamin B2 served as the colorant, imparting a yellow hue to the final film.

The following two methods were evaluated for incorporating the active ingredients:

Formula 1: Addition of actives and PEG before being added to the polymer mix.

Formula 2: Actives dissolved in water with PEG, then mixed into the polymer mix.

In both methods, water was used as the primary solvent for blending all components. The process map given as in 

. Post drying the films were cut into 2x2cms postage stamp size strips. As though both methods gave promising results, Formula 2 was selected for further testing parameters. Characterization and testing the final formula 2 films were evaluated using the following techniques:

Thickness uniformity was measured using a Positector 6000 thickness gauge.

Mechanical properties: Puncture/penetration test Assessed via texture profile analysis (TPA).

Assay of active ingredients: absorbance using ultraviolet-visible (UV-VIS) spectrophotometer (GENESYS 10S).Films (200 mg) were compared against standard solutions of each raw material.

Fourier transform infrared (FT-IR) spectroscopy was used to analyze both raw materials and the final dry Formula 2 films to confirm chemical integrity and compatibility.

Stability testing was conducted in a temperature-controlled chamber at 45 

Figure 1: Process Map for ODF Development. Figure courtesy of the authors.

Visually, the films from both formulas appeared uniform and exhibited a smooth finish. The final films from Formula 2 maintained a consistent thickness within the target range of 80-100 microns with weight of the film less than 100mg. Mechanical testing using a texture analyzer, demonstrated that the films possessed excellent mechanical strength (

Figure 2A. Quality metrics – Thickness and Mechanical Strength. FIgure courtesy of the authors.

Figure 2b. Figure courtesy of the authors

Figure 2C. Figure courtesy of the authors.

Analytical evaluations confirmed the identity and consistency of the films:

FT-IR spectroscopy revealed that the spectral profiles of the films matched those of the individual raw materials (

UV-VIS absorbance overlays showed alignment further validating the formulations (

Figure 3A. Assay and Identity of the Ingredients. Figures courtesy of the authors.

Additionally, the films exhibited excellent disintegration performance, dissolving completely in water within 30 seconds. Stability profile showed intact actives and identical to the control.

The project delivered a patient-friendly ODF that can deliver 100% DV actives in 200mg strip. The dosage can be adjusted based on the requirement. Through systematic formulation using a combination of synthetic and natural polymers, along with carefully selected excipients, the final films achieved desirable mechanical strength, uniformity, and rapid disintegration. Both formulation methods produced films that met critical quality attributes. Analytical techniques, such as FT-IR and UV-Vis spectroscopy, confirmed the presence and stability of active ingredients, ensuring the integrity of the final product. The films’ ability to dissolve within 30 seconds, supports the purpose. This study supports the potential of ODFs as a versatile platform for delivering vitamins, nutraceuticals, and pharmaceutical actives.

Gupta MS, Kumar TP, Gowda, DV, et al. Orodispersible thin film: A new patient-centered innovation. 

Journal of Drug Delivery Science and Technology

 October 2020 59, 101843 doi:10.1016/j.jddst.2020.101843

Orally dissolving films were optimized to deliver an energy/alertness nutraceutical blend for patients with pill fatigue or dysphagia. Solvent casting with low-temperature drying enabled incorporation of heat-sensitive vitamins using a hybrid polymer matrix of HPMC and high-methoxyl pectin with PEG, lactose, and sodium starch glycolate. A water-based premix of actives (vitamins B2, B6, C, and caffeine) with PEG improved incorporation. Final 2×2 cm films showed 80–100 µm thickness uniformity, strong mechanical performance, complete disintegration within 30 seconds, and 4-week stability at 45°C.

The aim of this study was to develop and optimize an orally dissolving film formulation containing a blend of active ingredients in a strategic combination of natural and synthetic excipients to achieve a balance between controlled actives release and rapid onset of action.  