Predicting process design spaces for spray drying amorphous solid dispersions

Abstract

Amorphous solid dispersions (ASDs) are commonly manufactured using spray-drying processes. The product quality can be decisively influenced by the choice of process parameters. Following the quality-by-design approach, the identification of the spray-drying process design space is thus an integral task in drug product development. Aiming a solvent-free and homogeneous ASD, API crystallization and amorphous phase separation needs to be avoided during drying. This publication provides a predictive approach for determining spray-drying process conditions via considering thermodynamic driving forces for solvent drying as well as ASD-specific API/polymer/solvent interactions and glass transitions. The ternary API/polymer/solvent phase behavior was calculated using the Perturbed-Chain Statistical Associating Theory (PC-SAFT) and combined with mass and energy balances to find appropriate spray-drying conditions. A process design space was identified for the ASDs of ritonavir and naproxen with either poly(vinylpyrrolidone) or poly(vinylpyrrolidone-co-vinylacetate) spray dried from the solvents acetone, dichloromethane, or ethanol.

Thermodynamic Balance vs. Computational Fluid Dynamics Approach for the Outlet Temperature Estimation of a Benchtop Spray Dryer

“…The Q loss determination can be avoided by assuming that the spray dryer operates adiabatically and without heat losses. This assumption is feasible in the case of industrial sites where the equipment is insulated and, thus, presents a low overall heat transfer coefficient [19]. In laboratory equipment, to help the development and to allow for internal flow visualization, the tower is made of glass with an emissivity value between 0.62 and 0.95, implying a high Q loss ; therefore, a radiation analysis should be performed [28].…”

“…Using modeling tools to obtain a DS can lead to an effortless scale-up with a better prediction of the final product properties, as proposed in a paper by Lebrun et al, where a DS that takes into account multiple critical quality attributes of the product has been performed [18]. Another example of the DS approach has been used for the development of an amorphous solid dispersion, in order to avoid risk of API crystallization and enhance its stability [19]. In spray drying, DS composite variables, formed by single parameters, are usually considered to allow two-dimensional representations of the DS.…”

Progress on COVID-19 Chemotherapeutics Discovery and Novel Technology

“…Lopinavir ( Figure 2 ( 3 )) and ritonavir ( Figure 2 ( 2 )) are commonly used in the clinical treatment of patients infected with human immunodeficiency virus (HIV) in the form of fixed-dose combination drugs [ 51 ]. The manufacturing process of ritonavir involves, firstly, the synthesis of the formazan ox-carbonyl derivative fragment, the n-hexane fragment, and the valine derivative fragment, followed by amide condensation of the three fragments [ 52 , 53 ]. Lopinavir requires (2S,3S,5S)-2-amino, the succinate salt of 3-hydroxy-5-(tert-butoxycarbonylamino)-1,6-diphenylhexane as the starting material, which is prepared via a three-step reaction of amidation, amino deprotection, and amidation.…”

Integrating Elastic Tensor and PC-SAFT Modeling with Systems-Based Pharma 4.0 Simulation, to Predict Process Operations and Product Specifications of Ternary Nanocrystalline Suspensions

“…where the y m term represents the mole fraction of the moisture (water) in the air, P is the air total pressure and P 0 is the equilibrium vapor pressure, dependent solely on temperature [46]. Conclusively, as demonstrated by Figure 7b, the validated design operational space of the SD by the input data indicated in Table 5 confirms that the in silico predictive results fit perfectly onto the associating experimental data [16], whereas the yellow narrow rectangular region (design space considered) demonstrates the area of interest with accuracy, constituting the criteria set for the responses fulfilled.…”