Preparation of Azithromycin Amorphous Solid Dispersion by Hot-Melt Extrusion: An Advantageous Technology with Taste Masking and Solubilization Effects

Abstract

Azithromycin (AZI) is one of the most commonly used macrolide antibiotics in children, but has the disadvantages of a heavy bitter taste and poor solubility. In order to solve these problems, hot-melt extrusion (HME) was used to prepare azithromycin amorphous solid dispersion. Preliminary selection of a polymer for HME was conducted by calculating Hansen solubility parameter to predict the miscibility of the drug and polymer. Eudragit® RL PO was chosen as the polymer due to its combination of taste-masking effect and dissolution. Moreover, the solubility was improved with this polymer. Design of experiments (DoE) was used to optimize the formulation and process, with screw speed, extrusion temperature, and drug percentage as independent variables, and content, dissolution, and extrudates diameter as dependent variables. The optimal extrusion parameters were obtained as follows: temperature—150 °C; screw speed—75 rpm; and drug percentage—25%. Differential scanning calorimetry (DSC) and Powder X-ray Diffraction (PXRD) studies of the powdered solid dispersions showed that the crystalline AZI transformed into the amorphous form. Fourier transform infrared spectroscopy (FTIR) results indicated that the formation of a hydrogen bond between AZI and the polymer led to the stabilization of AZI in its amorphous form. In conclusion, this work illustrated the importance of HME for the preparation of amorphous solid dispersion of AZI, which can solve the problems of bitterness and low solubility. It is also of great significance for the development of compliant pediatric AZI preparation.

The Antibacterial Properties of Nanocomposites Based on Carbon Nanotubes and Metal Oxides Functionalized with Azithromycin and Ciprofloxacin

“…The most important characteristics of the vibration bands for azithromycin, in accordance with the literature [ 44 , 45 , 46 ], are as follows: 3558 and 3485 cm −1 (O-H); 2971 and 2783 cm −1 (C-H); 1720 cm −1 (-C=O); 1638 cm −1 , 1458 cm −1 , 1378 cm −1 , 1343 cm −1 , 1281 cm −1 , and 1185 cm −1 (-C-O); 1082 cm −1 and 1051 cm −1 (R-O-R and C-N), 995 cm −1 , 900 cm −1 , 834 cm −1 , 795 cm −1 , and 730 cm −1 (C-H), 639 cm −1 and 573 cm −1 .…”

Contemporary Review on Solubility Enhancement Techniques

“…These particles have been observed to possess great potential for in vivo applications. Chang et al observed that the hydrophobic encapsulation of cur-cumin in egg white protein nanoparticles was enhanced, thus effectively decreasing its degradation rate and safeguarding its antioxidant activity when compared to nonencapsulated particles [97][98][99] .…”

“…With this variety of methods you will be able to ensure optimal performance in your drug application. The solubility of any drug is heavily determined by the chemical make-up and the components of its solution [18][19][20][21][22][23] .…”

A review of hot melt extrusion paired fused deposition modeling three-dimensional printing for developing patient centric dosage forms

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