Multiparticulate oral drug formulations are used for many different applications, most commonly to achieve modified drug release of a single API or multiple APIs with different release profiles. Pellets or spheres serve as inert cores to which one or more APIs are applied. A modified-release coating is then typically applied, and the coated pellets or spheres are filled into a capsule, sachet, or other delivery vehicle. Once administered to (or by) the patient, the modified-release coating dissolves under specific pH conditions to enable consistent release of the API at the desired location in the gastrointestinal (GI) tract.
Sustained-release products allow for the reduction of dosage frequency, simplifying treatment regimens, which in turn reduces the burden on patients and increases compliance, especially for patient populations that have difficulty taking medications. Incorporation of multiple APIs in one product helps to further increase ease of use for patients.
The equipment and sophisticated expertise required for the successful development of prototype multiparticulate solutions using pellets in particular is currently limited in the marketplace. Creating a high-quality drug product that provides consistent API release requires starting pellets (or spheres) of sufficiently high quality, uniform sphericity, and narrow particle size distribution.
Often, multiparticulate formulations are developed using APIs that are already marketed in order to offer a new patient benefit — often modified-release capability — and provide an alternative to the existing branded product.
A number of different substrates have been developed in pellet and sphere form for use in multiparticulate formulations. Sugar spheres are the most widely used starting materials, with a long history of use across applications. In many cases, however, there is a specific technical need for alternative substrates, such as microcrystalline cellulose (MCC) and tartaric acid.
With respect to the pellets/spheres themselves, there are three main critical quality attributes (CQAs) that enable the effective drug loading and coating of the particles: particle size distribution, sphericity, and friability. The particle size distribution must be fairly narrow, and the pellets must be as spherical as possible and must be able to withstand the process conditions involved in manufacturing the final drug product. All three properties can impact the release profile of the API(s). As a result, close attention must be paid during production of the pellets/spheres to ensure that the desired CQAs are achieved. It is also critical that formulators pay close attention to CQAs to ensure that the products they create are high functioning and reproducible, because not all manufacturers produce spheres with suitable CQAs.
MCC spheres are attractive for applications where the pellet must be inert, not friable, and smoother and more spherical. In addition, compared with sugars, MCC can be formed into much smaller particles that still retain good friability and sphericity. Smaller particles are typically preferred for multiparticulate formulations that contain higher drug loads or several APIs. Furthermore, MCC is widely used as an excipient and is recognized and accepted in the pharmaceutical industry, simplifying regulatory compliance.
Tartaric acid pellets (TAPs)/spheres enable the formulation of weakly basic APIs, which otherwise can be quite challenging because they tend to exhibit poor dissolution in the gastrointestinal (GI) tract. The tartaric acid provides a local acidic environment that facilitates dissolution of weakly basic APIs in higher-pH regions of the GI tract, even in modified- and controlled-release products.
ACTILLETS® MCC Microcrystalline Cellulose Pellets and TAP® Tartaric Acid Pellets from SPI Pharma are used to create modified-release drugs and multi-unit particulate systems (MUPS) when used as starter cores for drug layering and coating. ACTILLETS® MCC pellets have low friability, high sphericity, and smooth surfaces for consistent coating. TAP® tartaric acid pellets can be used to improve the solubility of weakly basic pharmaceutical actives.
Both types of pellets are manufactured using a process designed to generate highly robust pellets of high sphericity and very low friability. Notably, the particle size distribution of ACTILLETS® pellets is tightly controlled, and they are available in various particle sizes for use with different APIs in a variety of applications. TAP® Tartaric Acid Pellets are ideal for use with APIs that exist in the bitartrate salt form.
SPI Pharma acquired sole distribution rights for CELLETS® MCC pellets and TAP® tartaric acid pellets for North America, Latin America, New Zealand, and Australia from Glatt. The MCC products will be distributed under the ACTILLETS™ brand name in these regions.
SPI Pharma creates value by combining our technical knowledge with specialized materials to generate products designed to perform at the highest level in specific applications, focusing largely on patient-friendly formulations. An important aspect of the company’s growth strategy is to expand into adjacent technologies and markets that allow us to leverage that combination of resources and create new valuable solutions for our customers.
Modified-release, oral dosage formulations represent a technology and market directly adjacent to immediate-release oral dispersible formulations, which is an area of specialization for SPI Pharma. This market is growing at 6–8% annually, a growth rate much higher than that of most other technologies used for life cycle management of existing APIs. Given our longstanding formulation expertise and technical knowledge base, neutral cores and spheres — particularly high-performing spheres — are an ideal fit for a portfolio expansion. ACTILLETS™ MCC and TAP® products give SPI Pharma the ability to support the modified-release market with highly specialized, high-performing excipients.
Rebranding both the MCC and TAP® excipients as ACTILLETS™ products rather than just reselling them allows SPI Pharma to combine this exciting solution for modified-release and multiparticulate formulations with our specialized formulation expertise and other advanced excipient technologies. Formulation is always the key barrier to adoption, no matter how compelling a technology might be. Multiparticulate and modified-release dosage forms are no exception.
SPI Pharma is always focused on the concerns and pain points of the customer and on developing solutions to address these challenges. In the process, we seek to form long-term relationships with our customers that go well beyond simply selling them the ingredients that they require. Of course, for those customers that have relevant in-house formulation expertise, SPI Pharma is happy to provide ACTILLETS™ MCC and TAP® products by themselves. For customers that lack the specialized expertise needed to use these sophisticated excipients, SPI provides assistance in addressing the challenges of preparing loaded pellets/spheres and then formulating them into final drug products. Preparing the modified release pellet is only the first step — those pellets must then be matched with the right delivery system to ensure that the pellets/spheres reach the right location within the body for the API’s action.
Unlike other excipient manufacturers, sellers, and distributors that focus solely on the material, SPI Pharma is a highly specialized excipient company that collaborates with customers to ensure that the excipients we sell are used optimally and cost-effectively. With SPI Pharma, drug developers get access not only to ACTILLETS™ technology but to a portfolio of other innovative excipients that can be used in combination to provide unique formulation solutions. In addition, through our partnership with Glatt, we can offer additional expertise in making these different dosage forms and the processing that is involved in realizing their full potential.
SPI Pharma’s knowledge of mannitol and our Mannogem XL grades of this important excipient, combined with ACTILLETS™ pellet technology, put the company in a unique position in the market. Mannitol complements the pellet technology in many different modified-release applications. Mannogem XL grades, specifically, offer higher compactability and faster disintegration times than standard spray-dried or granular grades. They can be used as the binder for coated pellets/spheres in multiparticulate tablet formulations to ensure robust tablet formation combined with the appropriate disintegration time that allows release of the pellets/spheres and ultimately release of the API. Such tablets are highly complementary to oral dispersible tablets, formulations for which SPI Pharma already provides extensive excipient technologies and expertise.
SPI Pharma’s ambition is global, multi-material, and application-focused. While the current agreement regarding ACTILLETS™ MCC and TAP® products is limited to specific geographies, it will enable SPI Pharma to gain a foothold in the controlled-release market. Modified-release solutions leveraging the ACTILLETS™ technology and SPI’s knowledge will be developed for the regions covered in the agreement and shared with interested scientists, globally.
We welcome requests for information about ACTILLETS™ pellets/spheres from anyone anywhere in the world, not just people located in regions covered by this recent agreement. We are looking to drive interest in the use of MCC and TAP cores for the formulation of modified-release drug products, regardless of where the purchase of those materials occurs. We are willing to engage with anyone and connect them with the authorized distributors for their markets.
The partnership with Glatt is just the first example of moves SPI Pharma will be making going forward. The company hopes to announce multiple product launches and new partnerships annually in order to expand our product and service portfolios quickly. Look for more exciting news from SPI about innovations coming both from partnerships and as the result of internal development activities, all with the goal of offering more solutions for our customers.
In addition to ACTILLETS™ MCC and TAP® products, the agreement with Glatt includes distribution rights for Ibuprofen DC100, a 100% active granule from IPC produced without further excipients, enabling simpler, more cost-effective ibuprofen formulations. This specialty API expands SPI Pharma’s portfolio of APIs, which includes taste-masked ibuprofen and acetaminophen.
We are excited to explore various formulating opportunities with Ibuprofen DC100. Ibuprofen is one of the most widely prescribed APIs in the United States and Europe (with even greater nonprescription sales). It is a non-opioid pain reliever that is highly effective and is associated with relatively moderate liver toxicity. For these reasons, there are significant opportunities for growth in this market. Ibuprofen DC100 addresses some of the shortcomings of immediate-release ibuprofen, but SPI Pharma is looking to advance the technology even further.
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