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