18 Near-Infrared Spectroscopy in the Pharmaceutical Industry
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protein structures by creating aggregates or irreversible modifications. Several studies
have looked at the protein conformation during lyophilization and the interactions
with the lyoprotectant compounds [33].
18.3.3 Summary
While biological processes use water as a medium and water has a strong NIR absorptivity, a large body of work has been established, demonstrating the suitability of the
technique. Simplification of the modeling and sensitivity enhancement could help
NIRS support the development of robust processes and, when relevant, be employed
to monitor or control processes during manufacturing operations.
18.4 Small Molecules
Engineered to generate a particular therapeutic response, small molecules have been
the workhorse of the pharmaceutical industry. While more and more biological products are being brought to market, small molecules will remain a significant part of
the portfolio of pharmaceutical companies for the foreseeable future.
There are usually two main manufacturing steps in bringing a synthetic active
pharmaceutical ingredient to patients: the first consists in producing the small
molecule in large quantity with the desired properties; the second will take the API
and transform it in a form that can be supplied to the patients (tablets, capsules,
transdermals, creams) or used by medical professionals (injectables). The remainder
of the chapter will discuss how NIRS has been used in the support of these activities.
18.4.1 Drug Substance Manufacturing
The synthesis routes leading to the discovery of APIs are usually not optimized
for purity and manufacturing efficiency. Process chemists and engineers will often
develop a simplified and robust process while ensuring that the molecule retains
its safety, efficacy, and physico-chemical characteristics. The synthetic route must
ensure that all the raw material properties and unit operations that lead to the formation of the final drug substance are understood so that properties such as API particle
size and shape, form, impurity level, and yield are controlled during production.
A synthetic synthesis will involve combining raw materials, reactions with the
formation of intermediates, isolation of intermediates, and final product isolation.
For each step, the impact of temperature, pressure, steering rate (amongst other
parameters) on the solubility, and reaction kinetics will need to be carefully studied to
397
protein structures by creating aggregates or irreversible modifications. Several studies
have looked at the protein conformation during lyophilization and the interactions
with the lyoprotectant compounds [33].
18.3.3 Summary
While biological processes use water as a medium and water has a strong NIR absorptivity, a large body of work has been established, demonstrating the suitability of the
technique. Simplification of the modeling and sensitivity enhancement could help
NIRS support the development of robust processes and, when relevant, be employed
to monitor or control processes during manufacturing operations.
18.4 Small Molecules
Engineered to generate a particular therapeutic response, small molecules have been
the workhorse of the pharmaceutical industry. While more and more biological products are being brought to market, small molecules will remain a significant part of
the portfolio of pharmaceutical companies for the foreseeable future.
There are usually two main manufacturing steps in bringing a synthetic active
pharmaceutical ingredient to patients: the first consists in producing the small
molecule in large quantity with the desired properties; the second will take the API
and transform it in a form that can be supplied to the patients (tablets, capsules,
transdermals, creams) or used by medical professionals (injectables). The remainder
of the chapter will discuss how NIRS has been used in the support of these activities.
18.4.1 Drug Substance Manufacturing
The synthesis routes leading to the discovery of APIs are usually not optimized
for purity and manufacturing efficiency. Process chemists and engineers will often
develop a simplified and robust process while ensuring that the molecule retains
its safety, efficacy, and physico-chemical characteristics. The synthetic route must
ensure that all the raw material properties and unit operations that lead to the formation of the final drug substance are understood so that properties such as API particle
size and shape, form, impurity level, and yield are controlled during production.
A synthetic synthesis will involve combining raw materials, reactions with the
formation of intermediates, isolation of intermediates, and final product isolation.
For each step, the impact of temperature, pressure, steering rate (amongst other
parameters) on the solubility, and reaction kinetics will need to be carefully studied to