16 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, sprinklestyle 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
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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 decisionsupport tool during the early stages of the drug design process to improve acceptability and further understand ODT disintegration behavior”2.
SPI Pharma explores the advancements that are helping make drug dosage forms more patient-centric.
Over the last 20 years, formulations with a pleasant patient experience have grown into a significant portion of marketed medicines.
