Biphasic dissolution combined with modified cylinder method-A new promising method for dissolution test in drug-loaded nanoemulsions

Author(s)

Yukuyama, Megumi Nishitani ; Zuo, Jieyu ; Park, Chulhun ; Yousef, Malaz ; Bazan Henostroza, Mirla Anali ; Barros de Araujo, Gabriel Lima ; Bou-Chacra, Nadia Araci ; Lobenberg, Raimar

• Document type: Journal article
• Source: International Journal of Pharmaceutics; v. 632, p. 9-pg., 2023-01-06.

Abstract

Dissolution testing is important in assessing the in vitro drug release performance for oral administration dosage forms. However, currently, a simple and efficient in vitro test to investigate critical factors that may impact the drug release and bioavailability at the development stage of a drug-loaded nanoemulsion (NE) is lacking. Thus, in this study, we developed a new combined biphasic and modified cylinder (BP + MC) method to evaluate the dissolution profile of NEs. Flubendazole (FLZ), a Biopharmaceutical Classification System (BCS) Class II drug, offers a new prospective for drug repositioning for treating lung cancer and cryptococcal meningitis. We compared the drug release profiles of three different FLZ formulations (micronized as a suspension, loaded in NE, and solubilized in oil) by using three different methods (dialysis bag, modified cylinder method, and a new BP + MC method). The results showed potential higher drug release of FLZ from the suspension compared to FLZ-loaded NE at pH 1.2, and higher drug release from FLZ-loaded NE compared to other forms in octanol phase. These results correlate well with the in vivo test performed in mice carried out in our previous works. Further-more, the partition mechanism of the drug released from the NE is discussed in-depth in this article, as well as the advantage of drug-loaded NEs over other preparations in creating supersaturable conditions. Based on the re-sults, we provide new insights into how dissolution methods for a poorly water-solubility drug can be designed. Therefore, we present this new combined BP + MC method as a potential new discriminative dissolution test for future studies when developing drug-loaded NE and comparing with other dosage forms. (AU)

• FAPESP's process: 18/22713-2 - Study of Flubendazole repositioning for the treatment of lung cancer and MENINGOENCEFALITE employing oral lipid nanosystem
• Grantee: Megumi Nishitani Yukuyama
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/15981-0 - Repositioning study of flubendazol for the treatment of lung cancer and meningoencephalitis using oral lipid nanosystem
• Grantee: Megumi Nishitani Yukuyama
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 19/04998-2 - Nanocrystalline and amorphous solid dispersions formulations for improvement of antitumor therapies
• Grantee: Gabriel Lima Barros de Araujo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/08332-3 - NANOSTRUCTURED SYSTEMS WITH POTENTIAL APPLICATION IN TREATMENT OF NEGLECTED DISEASES
• Grantee: Nádia Araci Bou-Chacra
• Support Opportunities: Regular Research Grants