The effects of polymer carrier, hot melt extrusion process and downstream processing parameters on the moisture sorption properties of amorphous solid dispersions

Abstract

Objective The aim of this study was to evaluate the effect of polymer carrier, hot melt extrusion (HME) and downstream processing parameters on the water uptake properties of amorphous solid dispersions. Methods Three polymers and a model drug were used to prepare amorphous solid dispersions utilizing HME technology. The sorption-desorption isotherms of solid dispersions and their physical mixtures were measured by the Dynamic Vapor Sorption system, and the effect of polymer hydrophobicity, hygroscopicity, molecular weight and the HME process were investigated. FTIR imaging was performed to understand the phase separation driven by the moisture. Key findings Solid dispersions with polymeric carriers with lower hydrophilicity, hygroscopicity, and higher molecular weight could sorb less moisture under the high RH conditions. The water uptake ability of polymer-drug solid dispersion systems were decreased compared to the physical mixture after HME, which might be due to the decreased surface area and porosity. The FTIR imaging indicated the homogeneity of the drug molecularly dispersed within the polymer matrix was changed after exposure to high RH. Conclusion Understanding the effect of formulation and processing on the moisture sorption properties of solid dispersions is essential for the development of drug products with desired physical and chemical stability.

Preparation, characterization, and pharmacokinetics in swine of a florfenicol enteric formulation prepared using hot‐melt extrusion technology

“…However, these preparations are relatively high in cost for commercial production. With HME technology, the dissolution, and absorption properties, the drugs can be greatly improved by highly increasing the drug dispersion; furthermore, oral bioavailability can be significantly increased (Feng, Vo et al., ; Feng, Ye et al., ; Sareen et al., ), and the stability of microencapsulated drugs can be improved (Sarode et al., ).…”

“…Differential scanning calorimetry was performed on a PerkinElmer Diamond differential scanning calorimeter equipped with Pyris software (Shelton, CT, USA) (Feng, Vo et al., ; Feng, Ye et al., ). Samples were prepared by hermetically sealing 3–5 mg of the pure API, the physical mixture of FF and HPMCAS, and the milled extrudate in aluminum pans.…”

“…It integrates fusion, mixing, compression, and shearing in an axial space to blend materials at the molecular level. The dissolution and absorption properties and the oral bioavailability of drugs with high dispersion are greatly improved (Feng, Vo et al, 2015;Feng, Ye et al, 2015;Sareen, Mathew, & Joseph, 2012). HME can also increase the stability of microencapsulated drugs (Sarode, Sandhu, Shah, Malick, & Zia, 2013).…”

Effects of formulation composition on the characteristics of mucoadhesive films prepared by hot-melt extrusion technology

“…Although solvent casting is the most commonly used method for film preparation, it has many disadvantages, like multistep process, batch to batch variations, air entrapment and removal of solvent from the product is time‐consuming and tedious . On the contrary, HME is solvent free, adaptable to continuous manufacturing, and an economical process . HME involves heating the mixture of polymer blend and drug in a barrel and forcing it through a die to obtain granules or films .…”

“…[17] On the contrary, HME is solvent free, adaptable to continuous manufacturing, and an economical process. [18][19][20] HME involves heating the mixture of polymer blend and drug in a barrel and forcing it through a die to obtain granules or films. [21] The heat and the shear via the mixing elements ensure the mixing of all the components uniformly.…”