Oral solid dosage (OSD) is the most popular dosage form overall, because OSD products are convenient, flexible and cost-effective. Tablets and capsules, however, can be difficult for some people to swallow, which can have a direct impact on their likelihood of taking their medication.
The inability to swallow tablets —referred to as dysphagia — primarily presents itself in pediatric and geriatric patient populations, but all age groups can be affected; at least 40% of adults have reported problems swallowing medication, with 8% skipping doses and 4% stopping treatment as a result.1 Organoleptic and sensory properties (e.g., taste, mouthfeel and odor) and convenience — the ease of integration of medication into daily routines — are also important to patients.
According to a 2015 report, the industry has been slow to address the issue of patient difficulties with swallowing tablets.2 The U.S. Food and Drug Administration (FDA) published a guidance on the desired size, shape and other physical attributes of generic tablets and capsules in June 2015.1 In the document, the agency states that: “We believe that tablets and capsules can be effectively developed and manufactured to minimize swallowing difficulties, which can encourage and improve patient compliance with medication regimens.”
ODT products are targeted to disintegrate in the mouth within 30 seconds without the need for water. Chewable and fast-melt tablets disintegrate in the mouth within 30–60 seconds during chewing. ODP products are designed for rapid dispersal in the mouth and are typically offered in stick packs.
Potential additional advantages of these patient-friendly, orally dispersible dosage forms over tablets and capsules include faster onset of action and improved bioavailability, although this depends on the individual drug in the tablet.
For drug manufacturers, orally dispersible dosage forms can provide a marketing advantage, as a more convenient, patient-centric dosing option can increase patient compliance, enabling higher pricing and extended product life cycles, and may provide new access to greater patient populations. Pharmaceutical companies can also meet evolving regulatory expectations for the development of palatable, flexible and convenient dosage forms designed with specific patient populations in mind with orally dispersible products.
These benefits are driving a shift in the industry away from traditional tablets and capsules to dispersible products.3 Indeed, Persistence Market Research predicts that the global ODT market will expand at a compound annual growth rate (CAGR) of 11.5% from $11.4 billion in 2017 to approximately $27 billion by the end of 2025.3 Antipsychotic drugs will account for approximately 20% of revenues by the end of the forecast period, growing at a CAGR of 15.7%, while drugs for central nervous system diseases will have a 55% market share valued at $15 billion.
Formulation of orally dispersible medications requires specialized expertise in excipient technologies. ODPs must disperse in the mouth within seconds without agglomerating, while ODTs must disintegrate rapidly (generally under 30 seconds) while retaining appropriate robustness after tableting, remaining intact during the packaging process and in storage before being delivered to the patient. Both must be palatable, particularly if the medicine is designed for children.
Oral dispersal can be facilitated using water-soluble excipients, such as polyols like mannitol, and fast disintegration is facilitated by the presence of superdisintegrants.
In addition to taste, they must also provide a positive patient experience with respect to other organoleptic properties, such as odor, color and mouthfeel. Taste is a critical attribute of orally dispersible drugs, because the drug substance is released in the mouth as the product disintegrates. Many APIs have an undesirable bitter taste that must be effectively hidden or masked throughout the disintegration process. Flavor additives and specially designed taste-masking technologies are both used for this purpose.
An attractive mouthfeel is also important for orally dispersible drugs during their disintegration. Formulations based on insoluble excipients that produce a gritty or chalky sensation upon disintegration are unpleasant for patients. Any unpleasant experience can lead to poor medication adherence.
Once an optimal formulation is developed, orally dispersible products are typically manufactured using the simplest methods possible. ODPs are blended and then filled into sachets or stick packs. It is preferable that ODTs and chewable/meltable products are produced using direct compression. The excipients and drug substance are blended and then tableted.
For ODTs and chewable tablets made by direct compression, ensuring good flowability of the blend is essential; this is facilitated by having an appropriate and uniform particle size for the formulation. Content uniformity issues can arise for APIs that have been coated or complexed with another material to achieve taste masking, due to significant size differences between the coated drug and the excipients in the formulation. This can lead to segregation of the drug substance from the excipients and fillers during blending and/or tableting. These segregation challenges also apply to ODP product development.
Development of effective formulations containing high drug loadings can also be challenging. As the API level increases, it becomes more difficult to maintain the balance between dose form robustness, rapid disintegration and desired organoleptics.
One approach that formulators apply to overcome these challenges is to use a commercially available orally dispersible drug delivery platform to facilitate development and speed to market. SPI Pharma has developed different platforms based on co-processed excipients designed for use in patient-friendly, orally dispersible dosage forms.
These platforms (e.g., Pharmaburst® 500 and Advantol 300® for ODTs and Pharmasperse® 416 for ODPs) are based on polyols, such as mannitol and sorbitol, and are co-processed to optimize functionality when formulated in products for directly compressible, orally dispersible tablets and orally dispersible powders. These excipients are specifically designed for improved functionality with respect to disintegration and organoleptic properties.
Co-processing by SPI using our proprietary technologies results in the production of excipient platforms that have the requisite particle size for good flowability and appropriate high solubility for rapid disintegration and no grittiness. Mannitol has a negative heat of solution, thereby imparting a pleasant cooling sensation that adds to the desirable organoleptics. The overall result is excellent palatability with a creamy texture and mild sweetness.
Pharmaburst 500 has superior tabletability and rapid disintegration, as well as the organoleptic attributes already described, making it an ideal choice for designing ODTs — particularly where the API is required at relatively high drug loadings and has limited compactibility.
In summary, these co-processed, engineered excipients are designed to address the specific challenges presented by orally dispersible drug products and can significantly speed up development times as they enable simple formulation and process design.
SPI Pharma has extensive experience in taste masking and a breadth of knowledge regarding the performance of many different APIs in these types of drug products. We offer a line of taste-masked APIs through our Actimask® platform — based on proprietary technology. SPI also supplies Lubripharm® SSF, a lubricant with a less hydrophobic nature than magnesium stearate, which, when included in an ODT formulation with our platform excipients, helps achieve rapid disintegration, for use in orally dispersible formulations.
With our unique understanding of both the taste-masking API challenges and the excipient requirements, we are able to design the optimal formulation for most APIs to provide fast disintegration combined with robustness and desirable organoleptics.
SPI’s technical experts apply their formulation experience gained over years of working with different APIs to each new customer project. Understanding the range of potential solutions enables SPI to accelerate the development process and identify tailored solutions that meet specific formulation needs.
SPI supports customers around the world with formulation assistance through its Pharmasolutions drug development service. On a fee-for-service basis, we work closely with customers to develop dosage forms using our unique excipient and drug delivery systems. With sales in nearly 60 countries, SPI Pharma has a technical presence in Asia-Pacific, Europe, the United States and Latin America. We provide technical and customer service and support customized to the regional and local needs of our customers.
SPI delivers patient-centric solutions that provide increased convenience, compliance and flexibility targeted at patient groups who have specific and unique needs, such as children and the elderly, to improve patient outcomes.
Customers derive value from accelerated development of less common oral dosage forms that are inherently patient-friendly and palatable, attributes that are increasingly sought by regulatory agencies. They also benefit from the ability to create highly differentiated products in the marketplace that can enhance their life cycle management strategies.
A pharmacist, Graeme attained his Ph.D. in pharmaceutical technology from the University of Manchester, England. His 25 years of industrial experience were gained in a number of positions within the industry, in the fields of formulation development and drug delivery. He has also held senior technical positions at pharmaceutical solid form equipment and excipient companies. Graeme joined SPI Pharma in June 2017. His areas of expertise include oral dose form technologies and processes, novel soft capsule technologies, and drug formulation.