18 Near-Infrared Spectroscopy in the Pharmaceutical Industry
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18.4.2 Drug Product Manufacturing
Once a drug substance has been manufactured in sufficient quantity, the optimization
of the process that manufactures the drug product delivered to patients can start. The
form of the drug product can vary significantly based on the intended use and the
desired pharmaco-kinetic profile. Medicines for delivery to patients by health-care
providers will often be manufactured in the form of sterile products for intravenous
delivery. However, other means of drug delivery are necessary for patients to take
at home. Tablets are the most commonly used oral solid dosage forms because of
their convenience (which improve treatment compliance) and ability to change their
delivery profiles (immediate release or sustained release). But a visit to the pharmacy
will highlight the variety of delivery forms available, from creams and ointments to
inhalers, capsules, and transdermal patches to name a few.
Active pharmaceutical ingredients are often poorly flowing materials and so
merely pouring them directly in a capsule filling machine or tablet press would
result in variable dosage forms (not providing the patient with the right dose for the
intended therapeutic effect). To ensure the final drug product has the characteristics advertised on the label, the API is usually combined with inactive ingredients
(excipients) that will result in a better flowing material that can be processed at
high speed with the desired product attributes. When no other processing step than
mixing is necessary to ensure homogeneity and weight consistency, the process is
called direct compression. However, when the API is present in large quantity in
the formulation or has poor flowing properties, it may be necessary to granulate the
material (through physical means (dry granulation or extrusion) or using a solvent
and binder (wet granulation)) to obtain a free-flowing powder that can be processed
at high speed on a tablet press or encapsulator.
Because of the difficulty of working with powders and their ability to aggregate
or segregate, particular attention has to be given to the intermediate and final quality
attributes of the drug product. Near-infrared spectroscopy has been a tool of choice
for use in the manufacturing of oral solid dosage forms. Near-infrared light penetrates deeper than UV, Raman, or infrared light and rugged equipment is available
to measure the drug content during the manufacturing process. In addition, with the
transition of the pharmaceutical industry from batch to continuous manufacturing,
NIRS has become a tool of choice for in-line and in real-time measurements and
control of the manufacturing of drug products. In this section, examples of the use of
NIRS for the main unit operations involved in manufacturing tablets are provided.
18.4.2.1 Powder Homogeneity
This particular unit operation consists in mixing active and inactive pharmaceutical
ingredients to obtain a homogeneous mix that can be used for tablet/capsule manufacturing or for input to a granulation operation. The most important parameters
401
18.4.2 Drug Product Manufacturing
Once a drug substance has been manufactured in sufficient quantity, the optimization
of the process that manufactures the drug product delivered to patients can start. The
form of the drug product can vary significantly based on the intended use and the
desired pharmaco-kinetic profile. Medicines for delivery to patients by health-care
providers will often be manufactured in the form of sterile products for intravenous
delivery. However, other means of drug delivery are necessary for patients to take
at home. Tablets are the most commonly used oral solid dosage forms because of
their convenience (which improve treatment compliance) and ability to change their
delivery profiles (immediate release or sustained release). But a visit to the pharmacy
will highlight the variety of delivery forms available, from creams and ointments to
inhalers, capsules, and transdermal patches to name a few.
Active pharmaceutical ingredients are often poorly flowing materials and so
merely pouring them directly in a capsule filling machine or tablet press would
result in variable dosage forms (not providing the patient with the right dose for the
intended therapeutic effect). To ensure the final drug product has the characteristics advertised on the label, the API is usually combined with inactive ingredients
(excipients) that will result in a better flowing material that can be processed at
high speed with the desired product attributes. When no other processing step than
mixing is necessary to ensure homogeneity and weight consistency, the process is
called direct compression. However, when the API is present in large quantity in
the formulation or has poor flowing properties, it may be necessary to granulate the
material (through physical means (dry granulation or extrusion) or using a solvent
and binder (wet granulation)) to obtain a free-flowing powder that can be processed
at high speed on a tablet press or encapsulator.
Because of the difficulty of working with powders and their ability to aggregate
or segregate, particular attention has to be given to the intermediate and final quality
attributes of the drug product. Near-infrared spectroscopy has been a tool of choice
for use in the manufacturing of oral solid dosage forms. Near-infrared light penetrates deeper than UV, Raman, or infrared light and rugged equipment is available
to measure the drug content during the manufacturing process. In addition, with the
transition of the pharmaceutical industry from batch to continuous manufacturing,
NIRS has become a tool of choice for in-line and in real-time measurements and
control of the manufacturing of drug products. In this section, examples of the use of
NIRS for the main unit operations involved in manufacturing tablets are provided.
18.4.2.1 Powder Homogeneity
This particular unit operation consists in mixing active and inactive pharmaceutical
ingredients to obtain a homogeneous mix that can be used for tablet/capsule manufacturing or for input to a granulation operation. The most important parameters