Demand for liquid suspension product development and manufacturing is increasing as more drug companies seek to provide tailored products for pediatric and geriatric patients. Mikart is a trusted contract development and manufacturing partner with deep expertise in the development and production of suspension formulations. A new, state-of-the-art liquid suspension production suite has been added in response to client requests, positioning Mikart as an ideal outsourcing partner for support of accelerated liquid formulation development and manufacturing from R&D through commercialization and beyond.
Liquid Suspensions: An Attractive Alternative to Traditional Liquid Formulations
Liquid solution formulations, once referred to as elixirs, typically contain high concentrations of active pharmaceutical ingredients (APIs) dissolved in a liquid medium. These solutions are often favored for patients with dysphagia (difficulty swallowing), as well as pediatric and geriatric patients. However, direct exposure of the tongue to the API can lead to an unpleasant experience if the API itself has a bitter or otherwise unpleasant taste.
Liquid suspensions present several advantages over traditional solutions. Instead of being dissolved, the API remains suspended in particulate form within the liquid carrier. This reduces the interaction of the API with the taste buds, resulting in an improved taste profile. Additionally, the increased viscosity of suspensions enables quicker swallowing, preventing the liquid from permeating all corners of the mouth and reducing the lingering aftertaste often experienced with solution formulations.
For APIs that degrade in standard liquid formulation, it is possible to produce the drug product in powder form filled into either a sachet pouch or bottle. Reconstitution via addition of water and shaking creates a suspension. Such products can be prepared in multidose formats for reconstitution by a pharmacist or physician or in single-dose packages for preparation by patients directly.
Navigating Suspension Manufacturing Challenges
Manufacturing and packaging liquid suspensions are inherently more complex than solutions due to the nature of the formulation. While simple agitation suffices to dissolve APIs and excipients in liquid solutions, the manufacturing of suspensions involves more viscous liquids, thickeners, and suspending agents. Homogenization is crucial to ensure uniform dispersion of all ingredients and the API throughout the formulation.
Maintaining this uniform dispersion throughout all downstream manufacturing and packaging processes is critical to ensure consistent dosage in every primary packaging container. If segregation of the drug substance from the base occurs, the product may vary in potency, leading to super-potent or sub-potent doses. Once packaged, the integrity of this uniform suspension must persist through shipment and storage.
Despite efforts to maintain homogeneity, minor settling or segregation can occur over time. For this reason, suspensions should always be shaken vigorously before administration to ensure proper dispersion.
Leveraging Ion Exchange Technology
One of the recent innovations in suspension formulations is the integration of ion-exchange resins to enhance API properties. This technology has long been utilized in water purification and liquid chromatography for separating a range of chemical and biological molecules, including drug substances. The resins consist of charged polymers that can, depending on the nature of the charge (positive or negative) bind to oppositely charged or ionizable compounds.
In suspension formulations, APIs are mixed with ion-exchange resins in water, allowing the drug substance to attach to the resin particles. The water is then removed, and the particles are rinsed before being blended with the liquid base and other excipients to form the suspension. This approach not only enhances the stability of the API but also improves the taste profile through taste-masking and facilitates the development of sustained-release formulations. It has seen application in both OTC and prescription medications.
Mastering the Balance of Art and Science in Formulation
Formulating liquid suspensions involves a delicate interplay of science and creativity. The choice of excipients and liquid bases can significantly affect the performance of a formulation, and each has distinct properties that influence stability, bioavailability, and taste. The process often involves extensive trial and error, requiring numerous physical evaluations of various formulations to identify the optimal combination.
Extensive experience in formulating APIs into suspensions is invaluable, allowing for the careful selection of ingredients while minimizing experimental iterations. This not only reduces development time but also curtails the associated costs and resources, thereby accelerating the pathway to finalizing effective suspension formulations.
Ideal for the Growing Pediatric Market
While oral solid dosage forms remain the preferred method of administration, many patients, particularly pediatric and geriatric populations, find it challenging to swallow tablets or capsules. This has led to a significant increase in the demand for liquid dosage forms.
Regulations implemented a few years ago requiring products for children be formulated to meet their specific needs have driven pharmaceutical companies to convert adult oral solid dosage (OSD) medications into liquid formulations for the pediatric market. Similarly, the aging global population has led to a rise in the need for liquid products tailored to older adults.
Contract development and manufacturing organizations (CDMOs) like Mikart are consequently increasing pursuing 505(b)(2) projects involving conversion of existing OSD products into solution and suspension platforms, exploring different dosages to meet the specific needs of these populations. For instance, the antibiotic amoxicillin, frequently prescribed for bacterial ear infections, is now widely offered in a pink, bubblegum-flavored suspension. Beyond over-the-counter suspensions of common painkillers like ibuprofen and acetaminophen, prescription suspensions are also becoming more common.
Mikart: Blending Experience, Innovation, and State-of-the-Art Capacity
Mikart, a CDMO, brings years of experience in producing liquid drug products, including both solutions and suspensions. Their expertise spans traditional suspension formulations and newer technologies, like ion-exchange resins. This wealth of experience allows Mikart to streamline ingredient selection and expedite development timelines for a wide range of APIs.
Previously, manufacturing at Mikart involved separate buildings for production and packaging, which posed challenges for maintaining uniform suspensions. However, Mikart has since addressed this by investing in a new cGMP manufacturing suite located adjacent to their packaging lines. This facility enables robust production of liquid dosage forms in batches ranging from 50 to 4,000 liters, supported by temperature-controlled tanks and advanced technologies.
Once manufactured, suspension and solution products are placed into a transfer tank, immediately moved to the packaging line, and packaged into appropriate containers. As a result, Mikart now supports the manufacture of suspensions at R&D to commercial production scales.
In addition to typical bottle packaging, Mikart supports the production of unit dosage forms, including unit-dose cups and sachets, containing suspension products. This option allows clients looking to provide patient-centric products that consider ease-of-use and convenience for busy, active families and elderly patients who are on-the-go for a variety of reasons.
With years of experience and deep expertise in suspension formulation development, the ability to support projects from early-phase development through commercialization, our innovative Liquid and Suspension Suite for Oral Solution Program, and the capability to provide both traditional and newer packaging solutions, Mikart is a trusted outsourcing partner for companies seeking to offer differentiated suspension products.
