March 19, 2020 PAP-Q1-20-CL-004
Patient centricity is not only promoted by regulators, but it benefits global health. Patient-friendly dosage forms, such as orally dispersible tablets and powders, can be important tools in the practice of patient-centric drug development in terms of compliance, portability and delivery to sensitive populations (e.g., children and the elderly).
Orally dispersible medications are important patient-friendly dosage forms that require specialized expertise in excipient technologies. These medications must disperse rapidly in the mouth yet be robust enough to remain intact during the packaging, process, and storage. They must also provide a positive patient experience with respect to taste, sweetness, odor, color, and mouthfeel (organoleptics) to ensure adherence.
Excipients used in the formulation of orally dispersible drugs must be compatible with the API and must not negatively impact the stability of the drug substance. Formulators aim to match the particle size of the API with the excipients in the formulation. This is important for DC processes, in particular, where failure to do so will result in content uniformity issues caused by segregation during the blending, filling, and tableting processes. APIs that have been coated or complexed with another material to achieve taste masking can present increased challenges owing to their larger particle sizes, which can lead to sedimentation/segregation and subsequent out-of-specification blends or finished dose forms. Both very low and very high concentrations of API can create difficulties in achieving content uniformity and maintaining tabletability, respectively.
Mannitol is ideal for ODT formulations. It provides a cooling effect and smooth mouthfeel without being overly sweet. It has a high dilution capacity and low hygroscopicity. It also does not promote acid–base reactions or oxidation or react with primary amines, and it dissolves rapidly.
Spray-dried mannitol produces tablets with higher hardness than other types of mannitol at comparable compression forces and, with its higher surface area, works well as a base for ordered mixing with micronized APIs and low-dose formulations. Granular mannitol has a larger particle size with excellent flow and disintegration. It is ideal for use with taste-masked APIs and for imparting a softer texture in chewable tablets. Mannitol powder is suitable for use in wet granulation and lyophilization, offering shorter processing times due to its rapid drying properties.
Despite mannitol’s benefits, it can be difficult to formulate with, largely owing to its poor compactability. It can be challenging to formulate ODT and chewable products with pleasing organoleptic properties that also have good tabletability.
With core expertise in polyol chemistry, SPI Pharma has developed Mannogem® XL Mannitol products (spray-dried and granular) for use in multiple patient-friendly oral dosage forms. We have applied Mannogem XL technology to tackle the problem of mannitol’s poor compressibility, producing multifunctional, compendial grades of mannitol with superior binding and quick disintegration properties, greater compressibility and tight particle size ranges.
Mannogem XL Mannitol can produce tablets that exhibit higher hardness, faster disintegration, higher drug-loading capability, and significant improvement in friability. Less binder is required with this technology, and tablets can be made at lower compression forces. With these benefits, Mannogem XL Mannitol grades can make formulation of ODTs simpler, allowing the benefits of mannitol to be extended to applications beyond ODTs, such as chewables and even as a binder in tablets.
Mannogem XL Opal and Ruby offer all of the properties of standard compendial mannitol products combined with all of the benefits of the XL technology, including consistent performance and superior tabletability, enhanced manufacturing efficiency, reduced development time and costs, and formulation simplification.
Mannogem XL Ruby is a granular mannitol with a particle size of around 300 µm that exhibits much better overall performance compared with traditional 300-µm granular products, particularly in terms of tabletability. It is ideal for use in formulations with larger, coated (taste-masked) APIs that are prone to segregation. Mannogem XL Ruby provides excellent tabletability in a granular mannitol for the first time. Mannogem XL Opal is a 160-µm spray-dried mannitol with particle size that matches the typical size of APIs and other standard excipients. Both can be used for superior tabletability and the opportunity to reduce the use of external binders and/or disintegrants.
Drug manufacturers can use Mannogem XL Opal and Ruby mannitol products to drive productivity improvements from development to manufacturing, providing major gains in final dosage form consistency. Higher production rates are possible because tablet robustness is not compromised with increased press speeds. The high binding capacity makes these products more than just fillers; they are effective tablet binders, capable of producing quality, robust tablets at lower compression forces with low friability that can withstand the stresses associated with downstream unit processes.
Mannogem XL Opal and Ruby enable rapid and effective formulation of convenient, patient-friendly dosage forms, such as ODTs and chewables. Both have the compactibility to be used as a binder in formulations with moisture sensitivity or other incompatibilities with traditional binder systems. Patient compliance can be further increased with tablet size reduction and faster disintegration times. They broaden the options for overcoming issues with challenging formulations, such as content uniformity, poor API compressibility, and improved organoleptics. These new products expand the traditional operational envelope for mannitol. With their enhanced functionality, Mannogem XL Opal and Ruby enable formulators to develop sophisticated dosage forms, such as multiple unit particle systems (MUPS) and controlled-release (CR) ODTs, with the benefits of mannitol.
SPI Pharma’s treasure chest of mannitol excipients also includes Mannogem Emerald and Onyx, 25 µm and 50 µm mannitol powders. Mannogem Emerald and Onyx compendial powder mannitol have well-controlled and narrow particle size distributions for more consistent granulation. By broadening our portfolio with these two popular mannitol powders, we are helping our customers secure their supply chains and formulate with more confidence.
SPI Pharma’s extensive knowledge of polyol chemistry and singular focus on the pharmaceutical industry allows us to provide solutions for our customers’ processing needs. We know formulation can be challenging, and we develop and manufacture excipients of the highest quality to help formulators do their job better, facilitate the development of patient-centric formulations, and enable greater profitability for our customers.
SPI Pharma carries a broad portfolio of excipients that can be used in formulations with our mannitol products, such as our Actimask® taste-masked product line. In addition, as formulators develop more sophisticated ODTs, MUPS, and CR dosage forms, combining our advanced Mannogem grades with our other binders (sugars, starches) and Lubripharm®, Pharmaburst®, and various proprietary technologies, has the potential to realize significant synergies.
Our new Mannogem grades alone enable formulators to use mannitol to address a wider variety of challenges in the pharma industry. Combination platform approaches should allow mannitol to be linked through the value chain, providing even more application opportunities, including the prevention of common formulating problems and the development of a broader range of solutions that facilitate patient-centric formulations.
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.
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