Dosage Forms

4 mins 20/07/20
Author name: Yogesh Sadhale

Meeting the Demand for Multiparticulate Drug Products

The therapeutic advantages of multiparticulate formulations make them a popular drug delivery application. These small, discrete multi-unit dosage forms can be tailored for controlled and/or delayed targeted drug release depending on the polymer used for coating. Multiparticulates having different polymer-controlled release profiles can be blended to achieve a more complex release profile. Beads, sometimes called pellets, and mini-tablets are the most common forms of multiparticulates. These multi-unit dosage forms offer flexibility in target-specific delivery.

Beads usually are 1mm-2mm in size and have outstanding stability. Their spherical shape and compact structure allow for good flow behavior and make them easy to dose. Moreover, they have a uniform, low-abrasive surface. While a range of drug loading is possible, multiparticulates are ideal for controlled release application while ensuring drug absorption. The latter is ensured because multiparticulates disperse freely in the GI tract. This formulation advantage enables one to achieve the correct potency and to dose precisely. At Metrics, a project may call for us to dose beads coated with different APIs – fixed dose combinations, using different polymers for controlled release. We can dose three bead types on our IMA encapsulators.

Mini-tablets are typically 2mm to 3mm tablets produced on a rotary tablet press by direct compression. They can be manufactured by using multi-tipped tooling, which allow a high-throughput production. They can be coated using aqueous- or solvent-based films using fluidized-bed or pan coaters. They are versatile, with applications in pediatric dosing, patients who have trouble swallowing, and in cases where fast or flexible dose adjustments become necessary. This can make medication compliance easier for older patients and children.

Both beads and mini-tablets can be filled into a capsule or compressed into a larger tablet. A finished capsule or tablet can incorporate different mini-tablets, each formulated individually and programmed to release drug product at different places in the gastrointestinal tract. The combination of beads or mini-tablets into one compressed tablet or filled capsule can include immediate release, delayed release, or controlled release.

At Metrics Contract Services, we can produce immediate-release beads or modified release beads in different release formats. We also have the technology to process potent API. The manufacturing takes place in a dedicated fluid bed drying/encapsulation suite. Typically, a Glatt GPCG-1 or GPCG-10 is used during multiparticulate development. For scale-up and commercial manufacturing, a Glatt GPCG PRO 120 fluid bed processor is employed. The GPCG-120 is fit with two Wurster spray insert options for batch size flexibility. During pharmaceutical development encapsulation, the ever flexible IMA Zanasi 16 Plus is used. Commercial operations employ an IMA Adapta 100 high speed encapsulator, which has a high throughput capacity of up to 100,000 capsules per hour and also an integrated online checkweigher. Like the development space, the commercial operations at Metrics Contract Services have solvent rated suites and processing equipment for more options, giving ultimate versatility in batch size, to coat with a drug layer or a delay/sustained release polymer.

The development and manufacture of these multi-particulate formulations requires a high degree of expertise and know-how. Formulation development is fully supported by our Analytical Services group, which has more than 150 chemists. Our flexibility and capability enable us to offer a quick turnaround on development batches. We can tweak the formula as needed, with same-day testing to enable near-continuous processing.

Having the right equipment – both small and large scale fluid-bed and encapsulation technologies – allows Metrics Contract Services to meet our clients’ needs for multiparticulate drug products from the clinical phase all the way to commercial production. Metrics Contract Services’ one partner/one site approach ensures scientific continuity as well as a smooth tech transfer for its clients. It saves our clients’ time and cost while delivering a high quality product. If you have a upcoming project involving multiparticulate manufacturing, we would welcome the opportunity to discuss your needs.

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