More drug makers are turning to melt extrusion technology as a low risk way of formulating drug molecules with challenging profiles. A unique alternative has been developed that will add value to the formulation of both new molecular entities and established products.
A critical first step for success in drug development is choosing the right drug-delivery technology, whether the drug compound is a new molecular entity (NME) or reformulation of a mature product. Drug manufacturers must ensure that the delivery vehicle they select for their active pharmaceutical ingredient (API) will carry them to market safely, from development and regulatory, and patient acceptance standpoints.
 Drug makers have increasingly turned to melt-extrusion technology as an innovative, low-risk means of formulating drug molecules with challenging profiles (such as poor solubility) or specifically tailored release profiles. Meltrex®, an adaptation of conventional melt extrusion for pharmaceutical use and the proprietary technology of SOLIQS, enhances the bioavailability and release kinetics of formulations through a solvent-free, polymer-based process. It also provides a unique solution for poorly soluble molecules, and is a safe choice for formulating and developing from bench-to-batch scale.
Success story
The reformulation of the HIV protease inhibitor Kaletra® is a notable success of SOLIQS Meltrex technology. The two poorly soluble, BCS class IV active ingredients, lopinavir and ritonavir, were originally formulated as a soft-gel capsule. The Kaletra capsule had a high pill burden (six per day), had to be ingested with food, and required refrigeration to enable stabilisation. Reformulated by Meltrex as a tablet, Kaletra now boasts reduced inter-patient variability, a reduced pill count (four per day), room temperature stability, and can be taken with or without food.
The new Kaletra tablet formulated via SOLIQS Meltrex was a major improvement for patients using the drug. It was granted fast-track approval by the FDA, and now has over 350 manufacturing batches released and approved without one failure.
Manufacturing via Meltrex
SOLIQS Meltrex is a proven solid dispersion technology in which APIs are mixed with or dissolved in a patented polymer/surfactant combination to form a consistent drug-polymer matrix. This technology has the advantage of being a solvent- and dust-free process, which allows for a clean processing environment with a reduction in environmental pollution, explosion proofing and residual organic solvents. MeltrextherapeuticMeltrextherapeutic therapeutic advantages include improved dissolution kinetics, enhanced bioavailability – and efficacy – improved safety and the ability to customise release.
By selecting the optimal polymer composition, a hard and ‘plastic’-like tablet can be manufactured with low brittleness. These tablets cannot be crushed into a fine powder, which
reduces the potential for physical tampering.
Bioavailability
With Meltrex, the drug substance is stabilised by the molecular interactions between the drug and polymeric carrier. Enhanced bioavailability is achieved by the solid dispersion, in which the dissolved drug substance remains as a molecular dispersion in the hardened polymer. Formulations with embedded crystalline particles have been developed primarily to achieve customised controlled-release pharmacokinetic profiles. By varying the type of polymer used, manufacturers can achieve in vivo profiles ranging from those that reach peak blood levels within minutes to once-a-day formulations. Drug loads of 80% to 90% have been obtained with embedded crystalline formulations.
- Meltrex technology may also allow manufacturers to:
- Safeguard the feature profile, avoiding risk in regulatory and commercial process
- Gain improved tolerability and fewer side-effects
- Minimise interactions with food and alcohol, thereby limiting dose dumping
- Adopt a robust and elegant manufacturing process using standard, proven production equipment
- Formulate unique and directly shaped tablets
The SOLIQS team represents a partner with expertise
in feasibility studies, formulation technology, research and analysis,
scale-up, regulatory matters, and commercialisation.
In choosing SOLIQS
Meltrex, drug makers put themselves on the right path to commercialisation.
Company profile
SOLIQS is the drug delivery business unit of Abbott GmbH & C and was formed from a collaboration between Knoll and BASF to adapt extrusion technology for use in the formulation of pharmaceuticals. For more information, visit: www.soliqs.com
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