5 November 2014, Greenville, North Carolina: Carpenters measure twice and cut once. Pharmaceutical formulation developers should consider measuring multiple times and producing once, according to one Metrics Contract Services scientist.
Dr. Anshul Gupte, associate director of pharmaceutical development at Metrics, presented a case study at the American Association of Pharmaceutical Scientists annual meeting. In his poster presentation, Gupte discussed the merits of studying various classes of dry granulation binders using a range of roller compaction processing parameters – that’s the measuring part – in order to improve overall tablet quality and reproducibility – that’s the producing part.
Gupte presented his poster, “A Case Study on the Effect of Binder Type on Dry Granulation and Tablet Compression of a Model Formulation” Nov. 5 at 9:30 a.m. He conducted the study with one of his colleagues from Metrics, Dr. Michael Dehart, a formulation scientist, as well as Dr. Rahul Haware, associate professor of pharmaceutical sciences at Campbell University.
The study evaluated how different classes of dry granulation binders – in correlation to the roller compaction processing parameters – affected the granules and the subsequent tablet compression. The scientists tested three binders representing differences in plasticity and particle size, as well as the amount required to produce tablets with desired tensile strength and hardness – Avicel® DG, Avicel,® and Kollidon® VA 64 Fine.
Choosing acetaminophen as their active pharmaceutical ingredient (API), the scientists established three processing parameters for ribbon thickness, roller force and roller speed using the company’s Gerteis Mini-Pactor.® They then evaluated the following outputs to identify differences between the three binder groups:
• Milled roller compacted blends: Ratios of granules to fines, bulk and tap density, Carr index and flow properties, and
• Tablets: Hardness, thickness, friability and disintegration time.
“The beauty of working with a Gerteis is that it offers significantly improved capabilities to the dry granulation process through qualified gap and force measurements, being fully instrumented, constant ribbon density, easy scale-up to production, perfect gap seal system, and process data acquisition,” Gupte said.
Haware reviewed the raw data using principal component analysis, a statistical procedure. After analyzing the results from the different scenarios, the scientists found that the Kollidon VA-64 Fine blends exhibited the highest proportion of granules/fines and that the ratio was inversely proportional to the roller gap. Tablet hardness was inversely proportional to roller compaction force; the hardest tablets produced were those using Kollidon VA-64 Fine blends.
Gupte said the study showed him the value of examining the correlation between a dry granulation binder and the roller compaction parameters in order to create a working design space – thus allowing scientists to reproducibly manufacture the drug product and achieve needed specifications.
“From a formulation perspective, it all comes down to creating boundaries – edge of failures – around your formulation and processes and determining the working limits that will give you the desired product reproducibly,” he said.
Pharmaceutical scientists attending AAPS likely asked Gupte and his peers for their opinions about how “test driving” the Gerteis using different parameters and different classes of binders in formulations affected the final drug product. “When we acquired the Gerteis Mini-Pactor, we expected to extensively use it in projects that require densification but have moisture-related degradation,” he said. “The property of the binder itself is a completely different topic. This case study correlates the capabilities offered by Gerteis with choosing the right binder in your formulation. I think we’ll get questions about how a case study such as ours applies to the work we do for future clients.”
About Metrics Contract Services
Metrics Contract Services is a full-service pharmaceutical development and manufacturing organization serving clients worldwide. We deliver proven scientific and operational excellence for solid oral dosage forms. Our areas of expertise include quality formulation development; first-time-in-man formulations; Phase I-III clinical trial materials manufacturing; and analytical method development and validation services leading to commercial scale manufacturing. Our technical capabilities include highly potent, cytotoxic and unstable compounds; DEA Schedule II-V controlled substances; and products with poor bioequivalence, for which we offer an impressive propriety portfolio of advanced delivery methods. Located in Greenville, N.C., Metrics Contract Services is a proud member of the Mayne Pharma family. Learn more at http://www.metricsinc.com.
About Mayne Pharma
Mayne Pharma is a publicly traded specialty pharmaceutical company listed on the Australian Securities Exchange (ASX: MYX). The company develops and manufactures branded and generic product globally – either directly or through distribution partners – while applying its drug-delivery expertise for contract development and manufacturing services. Mayne Pharma has a 30-year track record of innovation and success in developing new oral drug delivery systems, and these technologies have been successfully commercialized in numerous products that have been marketed around the world. Mayne Pharma has drug development and manufacturing facilities in Salisbury, Australia, with expertise in formulating complex oral dose forms, including controlled substances, modified release products and inherently unstable compounds.
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Karen Stinneford, +1.919.833.9102 or karen.stinneford@maynepharma.com
Lisa Pendlebury, +61.419.548.434 or lisa.pendlebury@maynepharma.com
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