The next level of orally dispersible dosages
SPI Pharma explores the advancements that are helping make drug dosage forms more patient-centric.
Taking Orally Dispersible Dosages to the Next Level
In November 2019, it was heartening to read a New York Times article1 about the efforts of Cipla, an Indian drug manufacturer, to potentially save the lives of children living mostly in Africa. The simple switch of a combination HIV medication ritonavir–lopinavir–abacavir–lamivudine (Quadrimune) dosage into a strawberry-flavored, sprinkle-style form palatable for babies and toddlers, significantly improved compliance versus traditional tablets or an unpleasantly bitter syrup.
Over the last 20 years, formulations with a pleasant patient experience have grown into a significant portion of marketed medicines. Adhering to the regimen is as important a factor as the efficacy of a given medication. Development of patient-centric dosage forms addresses the psychological hurdle in the adherence portion of the efficacy equation. Developing a positive consumption experience for the patient includes characteristics such as taste, mouthfeel, tablet robustness, shape, size and presentation. Such properties are critical for patient-centric or more aptly, patient-preferred platforms which encourage drug regimen adherence and reduce missed dosages of less desirable forms. A formulator must be mindful of these properties when designing an Orally Dispersible Dosage form (ODD). Other practical considerations for manufacturing need to be considered; for example, formula stability, compressibility, friability, flow and blending.
SPI Pharma, along with academia and industry, have taken the approach of looking at this adherence challenge from the patient’s perspective to better understand the psychological obstacles and provide meaningful solutions in the ODD segment.
Products
The increasing demand for patient-preferred forms such as ODTs has led formulators to focus on specially designed excipients, such as co-processed platforms that allow drugs to be formulated quickly, often with only the addition of a lubricant and flavours/sweeteners. SPI Pharma was a pioneer in this area with the introduction of Pharmaburst 500, a product which enables high drug loading in an ODT while retaining fast disintegration. Compendial excipients such as mannitol can also be tailored for these uses. Mannitol has long been associated with ODDs due to its desirable sweetness, smooth texture, cooling sensation, and inertness. SPI Pharma’s Precious Gems Collection of mannitol allows significantly increased compressibility whilst still retaining its compendial status, pleasing palatability and fast disintegration. The high compressibility of such excipients is critical for direct compression processing, especially when a formula contains a significant portion of a poorly compressible drug. Furthermore, some drugs such as taste-masked versions or multi-particulate systems (MUPS) can cause segregation during processing due to higher particle size and/or density properties. SPI Pharma has addressed this with Mannogem XL Ruby, developing a high compressibility granular mannitol grade with similarly matched properties to overcome such issues.
Physiological Simulation
Traditionally, oral disintegration testing has been measured by the USP Disintegration Test. However, this rather one-dimensional test has little in common with the actual physiological conditions that occur in the mouth after an ODT is administered. There are various methods designed to better simulate such conditions. An example can be found in our recent work with the University of London which outlined a simulated mechanical tongue and oral cavity. The authors concluded that this “model could have the potential to be implemented as a decision-support tool during the early stages of the drug design process to improve acceptability and further understand ODT disintegration behaviour”2.
Taste-Masking
One of the main challenges for any formulation of ODTs is masking unpleasant drug taste. There exist a range of techniques to achieve this. Traditionally, these have consisted of applying barriers or pH-sensitive polymer coatings to drug particles or complexing the drug with other materials. However, these techniques tend to add significant bulk and increase mean particle size which limits the drug loading per dosage and can cause content uniformity issues. To improve this situation, we have developed an innovative aqueous coacervation technique that can add a minimal coating loading (<10%) while retaining good taste-masking properties. This Actimask technology has been applied successfully to acetaminophen and ibuprofen for effective taste-masking with minimal (approx. 8%) coating load.
Stickpacks
Stickpacks are gaining popularity in nutraceutical and pharmaceutical applications, partly for patient convenience, but they also enable formulators to utilise higher and more flexible drug dosages than ODTs. To be effective, such formulas need good flowability to both fill the package and subsequently pour- delivering a pleasant patient experience. Products such as Pharmasperse 416 - a granulated, preformulated flowable platform - can simplify development of these formulations. Flowable formulations can also find utility in larger sachet type packs or in applications where the finished formula may be sprinkled on to a foodstuff. This can increase palatability, especially in the case of bitter-tasting drugs, and allow easier administration to children or the elderly.
Drug Delivery
ODD formulas theoretically offer faster drug delivery by eliminating the stomach disintegration lag of traditional swallowed tablets. Depending on the drug properties, this can also open drug delivery via the oral cavity as an option with advantages such as fast drug uptake and potentially longer retention within the body (by avoiding hepatic first pass metabolism).
Future
As patient awareness of available dosage options and changing regulatory emphasis grow, the demand for more patient-centric formats will intensify. The FDA has emphasised a shift away from syrups/suspensions due to concerns that include dosing accuracy, portability and stability of liquids, as well as the Paediatric Investigation Plan requirement for new drug applications, all of which are driving manufacturers to consider all available solutions. With our long history of developing innovative patient-centric solutions, SPI Pharma has developed expertise in this area. Currently we are working on a directly compressible, sublingual platform with sub 10 second disintegration.
The collective goal in pharmaceuticals is to make sick people well - requiring the right medicine be delivered in the right quantity throughout the prescribed timeframe. By building on current and future technology advances, we can improve the patient experience and make a difference in patients’ lives.
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