(14e) Reprocessing of Spray Dried Dispersions: Minimizing Resources in Process Development and Dealing with the Possible Failure

Reprocessing
of spray dried dispersions: minimizing resources in process development and
dealing with the possible failure

T. Porfirio^1,2*,
I. Duarte¹, R. Ferreira¹, B. Henriques¹, J. Vicente¹,
V. Semião²

¹ Hovione Farmaciência SA, Sete Casas, 2674-506 Loures,
Portugal; *tporfirio@hovione.com

²LAETA, IDMEC, Mechanical Engineering Department, Instituto
Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisbon, Portugal

Spray
drying is a well-established manufacturing process to produce amorphous solid
dispersions to improve the bioavailability of poorly
soluble drugs. However, the scale-up of the process is
often considered a resource-intensive challenge requiring large quantities of
expensive drugs [1]. Therefore, the possibility of reprocessing spray dried
dispersions (SDD) is very appealing since it minimizes the material’s
requirements during the process development. Furthermore if the feasibility of
the reprocessing steps is demonstrated during development it can be applied
during commercial routine as risk mitigation strategy.

However,
the reprocessing can have significant potential to adversely affect the
identity, strength, quality, purity or other attribute of the drug and
excipients [2]. The reprocessing should be performed on the cases where there
is an improvement in one or more quality attributes without adverse effect on the
others. The drive of the present work is to understand the effect of successive
reprocessing steps on chemical and physical properties of spray dried solid
dispersions using different stabilizing polymers commonly
used in the production of amorphous solid dispersions.

Three
different systems were produced and reprocessed (as shown in Figure 1) using itraconazole
(ITZ) as model drug and HPMC E3, HPMCAS-MG and Copovidone as different stabilizing
polymers. After each spray drying step a sample was collected for analytical
characterization to assess the physicochemical attributes of spray
dried material viz. particle size, bulk density and content of residual solvents,
assay, and dissolution profile. The remaining spray dried product was reprocessed
to prepare the feed solution of the subsequent spray drying step. This study
carried out two reprocessing in order to understand when the material begins to
present modifications in its properties.

Figure 1 – Scheme
of the adopted method

All
the tests were performed in a lab-spray dryer equipped with a two-fluid nozzle
and using the same drying conditions (such as outlet temperature, drying gas
flowrate, feed flowrate and atomization flowrate). A solvent mixture of
dichloromethane and methanol was used to dissolve the material in a solid
concentration of 5 wt.%.

Placebo
tests with polymer-only were also performed to assess the physiochemical properties,
such as molecular weight, monomer content and heavy metal levels of the stabilizing
polymers. The same conditions were used as in the tests with active substance.

The
use of different formulations and placebos tests will clarify the role of the
polymer type on the SDD reprocessing.

Reference:

[1]
Hallow, D., Mudryk, B., Braem, A., Tabora, J., Lyngberg, O. & Tummala, S.,
2010. An Example of Utilizing Mechanistic and Empirical Modeling in Quality by
Design. Journal of Pharmaceutical Innovation, 5(4), pp.193–203. [2] Guidance
for Industry - Drug Substance Chemistry, Manufacturing, and Controls
Information, U.S. Department of Health and Human Services – Food and Drug
Administration