10 Drying in the pharmaceutical and biotechnology fields

A.S. MUJUMDAR and D.S. ALTERMAN

10.1 Introduction

This chapter provides a brief summary of the key dryer types used in the
pharmaceutical and biotechnology industries, followed by a discussion of
methods for removal of solvents from dryer exhausts. No discussion is
included of typical equipment for the removal of solid particulates such as
filters, cyclones, electrostatic precipitators or wet scrubbers from exhaust streams.
Drying of pharmaceutical and biotechnological products is used for a wide
assortment of chemical and biochemical materials produced in quantities
from large tonnages to very small batches. In general, the production
requirements are small but the quality constraints understandably very
stringent. Any form of potential risk of degradation from microbial attack,
thermal instability, oxidation, contamination with metallic compounds,
residual organic solvents etc. must be avoided. Dryer construction must be
polished stainless steel or enamelled iron. In view of the limited space
available, this chapter will focus mainly on the most commonly used dryers
for synthetic pharmaceutical as well as biotechnological products. For details
about the various types of dryers, their classification and selection, the
interested reader is referred to the Handbook of Industrial Drying. ll ) Further,
it should be noted that many of the dryers can also function as granulators;
this aspect is beyond the scope of this chapter.

10.2 Dryers for pharmaceutical and biotechnology products

Drying of pharmaceutical products is characterized by the following:

Highly heat-sensitive (thermolabile) products
Very-high-value products
Generally low production capacity requirements
No tolerance for contamination
Frequent presence of organic solvent (or mixtures)
High susceptibility to oxidative damage (requiring drying in inert atmosphere)
or risk of explosion/fire caused by the presence of either organic solvents
or explosive dusts
High sensitivity to moisture content.

E. Goldberg (ed.), Handbook of Downstream Processing

Chapman & Hall 1997
236 HANDBOOK OF DOWNSTREAM PROCESSING

Production of products in solid form (e.g. powders, tablets etc.) involves

drying at different stages of production viz. synthesis of intermediate products,
synthesis of drug formulations and manufacture of various dosage forms.
Besides conventional drying this often involves granulation, tabletting,
coating, application of multiple-layer coatings for controlled drug release etc.
Selection of production equipment and operating conditions for all these
operations must take into account the thermal sensitivity, dry kinetics, quality
etc. Cost of equipment and energy costs are generally of secondary importance.
Also, products are often produced and dewatered (using filters, centrifuges,
etc.) in a batch mode, while dryers used may only operate continuously (e.g.
spray dryers).
Drying of products of microbiological origin must be carried out with
extreme care to maintain their chemical and biochemical activity. Examples
of such products are various vitamins, enzymes, yeasts, molds, pesticides,
proteins, amino acids etc. Drying of, for example, antibiotics, enzymes, amino
acids, require that the product retains a high level of activity after drying.
In the drying of yeasts, it is important to minimize destruction of the
microorganisms during thermal drying. Strumillo, Markowski and Adamiec
have reviewed the main quality constraints in terms of the chemical,
biochemical and physical changes in bioproducts during drying.[2] Although
beyond the scope of this chapter, it is important not to consider the drying
operation in isolation. Non-thermal dehydration processes such as filtration,
centrifugation, ultrafiltration etc. should be considered in conjunction with
drying.
Fermentation broths are suspensions of biomass with some components
partly dissolved as a solution or gel. Most bioproducts are biopolymers
consisting of proteins or protein-like compounds. Their properties depend
upon how water binds to the molecules. Strumillo and co-workers group
bioproducts into two categoriesP]
Group 1: water acts as life medium for microorganisms (e.g. yeasts,
bacteria), or as reactant (e.g. enzymes)
Group 2: water is a solvent (e.g. vitamins, antibiotics, steroids etc.).
For group 1 products, the final moisture content must be such as to achieve
the state of anabiosis, in other words a reversible form of life of dried
microorganisms, which depends on the final moisture content. This must be
determined experimentally.
Another characteristic of bioproducts is their xerostability in addition to
their thermostability. Xerostability refers to their sensitivity to moisture
(water) content. Both are determined experimentally in order to select the
drying conditions to maintain viability of the product. Generally, products
of group 1 are very thermolabile and a maximum product temperature of
40C is suggested on the basis of data from scientific literature. For very