Development of a small-scale spray-drying approach for amorphous solid dispersions (ASDs) screening in early drug development

Abstract

Development of a small-scale spray-drying approach for amorphous solid dispersions (ASDs) screening in early drug developmentThe present study details the development of a small-scale spray-drying approach for the routine screening of amorphous solid dispersions (ASDs). This strategy aims to overcome the limitations of standard screening methodologies like solvent casting and quench cooling to predict drug-polymer miscibility of spraydried solid dispersions (SDSDs) and therefore to guarantee appropriate carrier and drug-loading (DL) selection. A DoE approach was conducted to optimize process conditions of ProCept 4M8-TriX spray-drying to maximize the yield from a 100 mg batch of Itraconazole/HPMCAS-LF and Itraconazole/Soluplus 40:60 (w/w). Optimized process parameters include: inlet temperature, pump speed, drying and atomizing airflows. Identified process conditions derived from the DoE analysis were further i) tested with Itraconazole, Naproxen and seven polymers, ii) adapted for small cyclone use, iii) downscaled to 20 mg batch production. Drug-polymer miscibility was systematically characterized using modulated differential scanning calorimetry (mDSC). Spray-drying was identified as a well-suited screening approach: mean yield of 10.1 to 40.6% and 51.1 to 81.0% were obtained for 20 and 100 mg ASD productions, respectively.Additionally, this work demonstrates the interest to move beyond conventional screening approaches and integrate spray-drying during screening phases so that a greater prediction accuracy in terms of SDSDs miscibility and performance can be obtained.

Advanced 3D Electrospinning “Xspin” System: Fabrication of Bifiber Floating Oral Pharmaceutical Scaffolds for Controlled Drug Delivery

“…DOE modeling was conducted by using the custom design platform in JMP 16 software developed by the SAS institute. As seen in Table , each process factor was studied at four levels while the inner needle diameter was included in the DoE as a numerical factor (two levels) . The model parameters specified as a traditional response surface design (RSM) are listed as applied voltage (kV) and RS, flow rate (mL/h) and RS, gap distance (cm) and RS, nozzle diameter (gauge), applied voltage (kV)·applied voltage (kV), applied voltage (kV)·flow rate (mL/h), flow rate (mL/h)·flow rate (mL/h), applied voltage (kV)·gap distance (cm), flow rate (mL/h)·gap distance (cm), gap distance (cm)·gap distance (cm), applied voltage (kV)·nozzle diameter (gauge), flow rate (mL/h)·nozzle diameter (gauge), and gap distance (cm)·nozzle diameter (gauge).…”

“…As seen in Table 2, each process factor was studied at four levels while the inner needle diameter was included in the DoE as a numerical factor (two levels). 28 The model parameters specified as a traditional response surface design (RSM) are listed as applied voltage (kV) and RS, flow rate (mL/h) and RS, gap distance (cm) and RS, nozzle diameter (gauge), applied voltage (kV)•applied voltage (kV), applied voltage 3) were collected using a modular NicoletTM iSTM 50 FTIR system (ThermoFisher Scientific, Waltham, Massachusetts, USA). About 20−25 mg of the samples were analyzed for percentage transmittance from 4000 to 400 cm −1 at a resolution of 4 cm −1 and 64 scans per run.…”

Analytical and Computational Methods for the Determination of Drug-Polymer Solubility and Miscibility

“…Forster et al have reported the composition dependent presence of single or multiple T g values in the system of lacidipine and indomethacin with PVP . Apart from the presence of multiple T g values, reports also state the presence of a single T g as a sign of the molecularly dispersed ASD. ,− This is one of the commonly used qualitative predictors of drug-polymer miscibility with more than 50 instances in the reviewed literature. In a most recent report, Blasi et al have reported the presence of multiple T g values for ASD with ketoprofen content more than 35% w/w in poly­(D, L-lactide- co -glycolide) …”