DESIGN OF AMORPHOUS SOLID DISPERSIONS FOR THE SYNCHRONIZED RELEASE OF TWO DRUGS

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DESIGN OF AMORPHOUS SOLID DISPERSIONS FOR THE SYNCHRONIZED RELEASE OF TWO DRUGS

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Li, Jinghan

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2021-12

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Abstract

Purpose: To develop an amorphous solid dispersion (ASD) design strategy for poorly water soluble drug combinations.Methods: Using sulfamethoxazole (SMZ) and trimethoprim (TMP) as the model drugs, a mixture of SMZ and TMP at weight ratios of 5:1 and 1:5 were formulated into ternary ASDs with an aminoalkyl methacrylate copolymer, Eudragit® E (EDE), and polyacrylic acid (PAA), respectively. The ASDs were characterized by thermal (differential scanning calorimetry, DSC), spectroscopic (dielectric and infrared spectroscopies, DES and IR) and X-ray diffractometric (XRD) techniques. The dissolution performance was evaluated under non-sink conditions using USP dissolution apparatus II method. Results: Ternary ASDs were successfully prepared by solvent evaporation. Analyses of the glass transition temperature data of the binary (drug-drug) and ternary (drug-drug-polymer) systems implied strong drug-drug and drug-polymer interactions. The interactions resulted in a reduction in molecular mobility, evident from the increase in the structural (α-) relaxation time. The ionic SMZ-EDE and TMP-PAA interactions were characterized using IR. The ternary ASDs exhibited substantial enhancement in drug dissolution when compared with the crystalline mixtures. The ternary ASDs exhibited synchronized release. Conclusion: The drug-drug and drug-polymer interactions improved the physical stability of the ternary ASDs by reducing molecular mobility. The proposed ASD design strategy could be a potential approach for the solubility enhancement of drug combinations with poor aqueous solubility.

Keywords

amorphous solid dispersion

coamorphous system

dissolution

fixed-dose combination

molecular mobility

synchronized release

Description

University of Minnesota M.S. thesis. December 2021. Major: Pharmaceutics. Advisor: Raj Suryanarayanan. 1 computer file (PDF); xi, 55 pages.

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Li, Jinghan. (2021). DESIGN OF AMORPHOUS SOLID DISPERSIONS FOR THE SYNCHRONIZED RELEASE OF TWO DRUGS. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/252471.

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