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Bioavailability enhancement presents one of the most interesting challenges in the way aseptic spray drying projects are approached. With more drug candidates emerging that need aseptic processing to meet bioavailability targets through faster dissolution rates, the level of interest is mounting from pharma companies and biotech firms alike.
The challenge with slow or inconsistent dissolution rates is well documented. With all pharmaceuticals, particularly slow-release drugs, the industry is striving to control the rate and extent to which the unchanged drug is absorbed. Some drugs can be challenging in the way they are reconstituted and absorbed into the body. Those with poor bioavailability may need increased dosage rates with likely unwanted side effects as well as product waste.
One of the tools in addressing these challenges is particle engineering, but the right facilities need to be in place in the manufacturing process. Aseptic spray drying (ASD) is the process whereby a liquid product is introduced to hot gas, creating an injectable-grade dried powder under wholly aseptic conditions. It is similar to traditional pharmaceutical spray drying, using cleanroom conditions, but with each step in the process being conducted aseptically, it eliminates the terminal sterilization step.
ASD can be compared to the process of lyophilization, or freeze drying, in that both produce a dried pharmaceutical powder from liquid. However, lyophilization lacks the enabling factors that ASD offers, such as the ability to engineer unique particle characteristics. Moreover, the gentle processing conditions in ASD give far more scope to engineer particles with desirable characteristics.
The secret lies in the process. APIs are mixed with water-soluble glass formers and aseptically spray-dried as solid, non-crystalline glass, to produce a highly polished microsphere in which the product is immobilized and stabilized. The resulting product can be either presented as an instantly reconstituting powder or a ready-to-inject format by suspending the microparticles within a non-aqueous liquid. These liquids are typically injectable grade liquids, such as low-density metabolizable oils.
A critical level of expertise is needed during spray drying. At Nova Laboratories, patented hollow microspheres (known as aerospheres) can be manufactured to create a thin shell wall around the API. This approach has been shown to produce dry powders with increased dissolution rates up to tenfold in some cases compared with conventionally spray-dried powder.
These aerospheres are created using a delicate process that involves adding blowing agents. The aerospheres have larger surface area and therefore, dissolve faster than microspheres. Any desired presentations can be configured at the feasibility stage for bespoke processing setups to be established and product characteristics tailored accordingly. Trials have shown that this technology can be successfully applied to many pharmaceutical preparations including live and non-live vaccines, insulin, monoclonal antibodies, recombinant growth hormones, proteins, enzymes, and nucleic acids.
Nova Laboratories’ VitRIS technology (vitrified readily injectable suspension) has been used to create a stable, ready-to-inject suspension that does not require any extra reconstitution steps at the point of use. Based on the same aeorospheres platform, it produces a dry powder that dissolves instantly upon reconstitution. Nova Laboratories has also developed HydRIS (hypodermic rehydration injection system), a platform that enables spray drying of a mixture of amorphous, glass-forming sugars onto a filter paper-like membrane, which is then enclosed in a plastic casing with ports at either end for a needle and syringe. When needed, liquid secured in the syringe floods the device to reconstitute the dried material. Both these platforms are examples of particle engineering technologies.
About the Author
Sam de Costa, PhD, is program manager for thermo-stabilization and aseptic spray-drying at Nova Laboratories.
Article DetailsPharmaceutical Technology
Vol. 39, No. 2
Citation: When referring to this article, please cite it as S. de Costa, “Particle Engineering for Bioavailability Enhancement,” Pharmaceutical Technology 39 (2) 2015.