Case Study

Microcaps Exceeds Stringent Requirements Beyond Taste Masking

By Luigi Boltri, Senior Director, Pharmaceutical Sciences, Business Support & New Technologies, Adare Pharma Solutions

Improving Flow Characteristics for APIs and Diluents in Pharmaceutical Formulations

The Challenge

A particularly bitter pediatric macrolide in powder form was brought to Adare for needs beyond just taste masking. The API also needed:

  • Fast release due to a narrow absorption window
  • A smooth syrup mouthfeel acceptable to children and infants
  • Over seven days of taste masking after suspension
  • Drug loading suitable for its high dose

The Solution

Our scientists paired the API with Adare Pharma Solutions’ Microcaps taste-masking excipient and were coated with a pH-dependent polymer. Rapid release was demonstrated in vitro and in vivo testing, achieving the targeted bioequivalence. The API’s particle size distribution (PSD in the range of 100-200μ) remained virtually the same minimizing any possibility of a gritty mouthfeel while also achieving over 10 days of taste masking in extemporary suspension. A high drug load of up to 70% was also achieved.

The Outcome

Adare’s double coated Microcaps particles were combined with an excipient mixture providing the appropriate pH and palatability to the extemporary suspension. By pairing the API with Adare’s industry leading Microcaps technology all requirements were met and, in most cases, exceeded.

“Adare technologies are incredibly robust and have the ability to solve more than one issue at a time. I firmly believe this is due to Adare’s culture of anticipating patients’ needs and our desire to ensure medications are a positive part of their care.” — Luigi Boltri, Senior Director, Pharmaceutical Sciences, Business Support & New Technologies

Adare Pharma Solutions is a global technology-driven CDMO providing end-to-end integrated services, from product development through commercial manufacturing and packaging, with expertise in complex oral formulations. Adare’s specialized technology platforms provide taste masking, controlled release, solubility enhancement, and patient-centric dosing solutions. With a proven history in drug delivery, Adare has developed and manufactures more than 45 products sold by customers worldwide.

Specialized Technologies:

The Parvulet® Technology is a patient centric dosage solution that enables a solid powder or tablet to convert to a semi-solid in the presence of water within thirty seconds. The final dosage is easily administered, as a soft food like texture, ideal for pediatric and geriatric populations (including those with dysphagia).

Microcaps® Taste Masking Technology achieves uniform and efficient coating of drug particles by a combination of coacervation (phase separation) and spray coating to build polymeric membranes of varying porosity and thickness. The completely encapsulated particle allows for a pleasant mouthfeel without an aftertaste. The Microcaps technology can be applied to multiple dosage forms and immediate and modified release profiles.

AdvaTab® Orally Disintegrating Tablets (ODTs) incorporates coated or uncoated drug particles that are uniformly dispersed in a low-moisture, rapidly disintegrating matrix. Each ODT is formulated to achieve an acceptable taste and desired release profile. AdvaTab® technology is ideal for patients who have difficulty swallowing, pediatric, geriatric, and dysphagic patients. This technology can be combined with Microcaps® and Diffucaps® to create IR or controlled-release ODTs.

Diffucaps® Customized Release Technology has the flexibility to incorporate functional, release-controlling polymers or protective coatings onto drug-layered cores, granules, or crystals. This allows for easy adjustment of both dosage strength and dissolution profile to achieve the desired in vivo pharmacokinetic profile. Beads can have different release profiles, different active ingredients, or both all in one product.

MMTS™ Multi Mini Tablet System Customized Release Technology combines the simplicity of a tablet formulation with the flexibility of multiparticulate dosage forms with high drug-loading capability. Adare has developed Ultra Microtablets—a smaller standard of tablets targeting diameters in the range of 1.2 mm to even 1.0 mm. The small size facilitates the development of products that can offer multiple drugs or varying release profiles within a single capsule.

The DIFFUTAB® technology is an effective solution for targeted drug delivery through customized and sustained release. The technology assists the development of high-dosage and sustained release products for once-daily administration. A matrix tablet is coated with functional polymers, followed by a blend of hydrophilic and hydrophobic polymers. Layered erosion and diffusion of the drug matrix tablet result in a controllable release.

ORBEXA™, a solvent-based granulation and extrusion technology is applicable for capsules and single unit sachets. The granulation spheronization and extrusion techniques produce beads of controlled size and density. The beads are coated with functional polymers to provide high drug concentrations and additional rates of control. The technology’s high-speed process can accommodate sensitive molecules like proteins and are suitable for high drug loading.

The Optimμm® technology creates microspheres with high drug loading suitable for taste masking, enteric coatings, and extended release oral applications. The technology is capable of producing single- or double-layer particles in one manufacturing step, lending to cost-effective creation of palatable dosage forms, which mimic traditional tablets, pills, and capsules. The Optimμm® technology allows for tremendous control over release rate and dosage form properties. This technology is ideal for oral small molecules, nutraceuticals, agricultural applications, flavorings, and heat stable molecules.

The Stratμm™ technology, for injectable delivery, allows for precise control of particle size and composition enabling predictable injectable performance, which is critical for self-administration, extended release, and modified release applications with a narrow therapeutic index. Unlike other encapsulation techniques, Stratμm™ is capable of producing single- or double-layer particles in a one manufacturing step, lending to creation of next-generation “pulsatile” release formulations or extended release formulations. This technology requires lyophilization and is ideal for injectable small molecules, proteins, peptides, vaccines, and heat-labile molecules.

The Unisun® technology combines the use of encapsulated or free drug, along with a fast-film forming agent, which allows for low-cost, long-acting intratympanic delivery of a therapeutic. The technology allows for less frequent administrations than current therapies and is capable of sustaining drug levels in the inner ear cochlea for weeks. The technology can be used inject and set up highly concentrated depots of a drug and is ideal for small molecules, proteins, peptides, and vaccines.