Pediatric Formulations: Technical and Regulatory Considerations - Pharmaceutical Technology

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Pediatric Formulations: Technical and Regulatory Considerations
Leading experts share their perspective on the specialized requirments when developing a pediatric formulation and examine dosage forms that can be used for this patient class in this roundtable moderated by Patricia Van Arnum.

Pharmaceutical Technology

Thin-film technology

By Martha S. Sloboda, business manager with ARx LLC, a subsidiary of Adhesives Research.

The oral thin film (OTF) platform is a proven and accepted form of drug delivery for pediatric products. Its premeasured format provides an accurate and easily ingested dose without water that allows for portable and convenient "give and go" administration by a parent or caregiver. Patient compliance can be improved because of an OTF's ease of administration and subsequent difficulty in expectoration. The dosage format offers flexibility in base chemistry and base formulation development from raw material selection to final packaging configurations as well as an established and well-understood manufacturing path. Based on the continuous nature of production, formulators can also approach pediatric films as either unique, single-product formulations, or as a dosage modification of a preexisting product.

Tolerability and disintegration. Beyond efficacy, most OTF development for pediatric products focuses on two key attributes: tolerability and disintegration. Depending on the age range, region, and marketing needs, formulators can uses various flavors and compendial excipients to create a child-friendly formula. They can also choose to develop dye-free and alcohol-free products, add sensory components such as heating or cooling sensations, and/or modify texture. Different taste-masking approaches can be incorporated, and the dosage unit area can be modified to hit specific taste and disintegration profiles ranging from less than five seconds to multiple minutes. Additionally, dissolvable films may be formulated to demonstrate adhesion properties for use with other devices currently used by younger populations to deliver medications or vitamins. With a standard active pharmaceutical ingredient (API) loading level of 50% of the final unit mass and an adjustable final unit area, formulators have a lot of latitude in both how much API can be loaded and how other product attributes can be tailored for each product.

Figure 3: Examples of thin films for pediatric use. (FIGURE 3 IS COURTESY OF ADHESIVES RESEARCH)
Other approaches in OTFs . Another approach to development is to leverage higher-dose, preexisting formulations for pediatric populations. Dissolvable films are currently manufactured as a continuous roll stock that is unitized during final packaging. With this approach, the packager cuts the film strip to an alternative size to achieve a different dose. For example, a 10-mg dose could become a 5-mg dose by halving the unit size. This approach is attractive because only one formulation is developed, but two or more products and dosage forms can be marketed (see Figure 3). Examples of this approach have been launched in the pediatric market, including cough/cold and gastrointestinal products.

Precision-coating techniques derived from transdermal and filled-pad production translate base chemistries into final dosage units with unit tolerances as tight as 2.5% around the potency target. Specialized coat weight monitoring systems and liquid deposition techniques enable any OTF product to hold and maintain consistent cross and downstream uniformity during manufacture. These manufacturing approaches are well understood and controlled, enabling robust, efficient development from bench to commercial scale.

Table III: Examples of commercially available over-the-counter thin-film pediatric products. (TABLE III IS COURTESY OF ADHESIVES RESEARCH)
The flexibility in base chemistry combined with an established production process enables formulators to present a new platform to the patient. From a materials-selection standpoint, the OTF format provides formulators with the flexibility to add or omit ingredients that are more or less desirable for pediatric populations while still producing a scalable product. Table III provides examples of commercially available thin-film over-the-counter pediatric products.

The dose accuracy, ease-of-use, convenience, and potential for improved compliance of dissolvable films continue to drive new formulations and applications for pediatric populations. New programs are emerging for topical, transdermal, and oral modified release pediatric products. In addition, OTFs have the potential to extend product life cycles for approved oral APIs via a simplified filing path such as a 505 (b)(2). OFT's flexibility in base formulations make them a viable strategy in pediatric formulations.


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