Development of a self-emulsifying delivery system N-(adamant-2-yl)-N-(para-bromophenyl)amine (adamantylbromophenylamine) in the form of a medicinal drug for oral administration. Part 1

Background. The poor solubility of active pharmaceutical ingredients in aqueous media poses a serious challenge to drug development due to their low absolute oral bioavailability.

Objective − development of a self-emulsifying drug delivery system (SEDDS) of adamantylbromophenylamine in the form of a pre-emulsion concentrate.

Materials and methods. To develop model formulations of adamantylbromophenylamine SEDDS pre-emulsion concentrate, excipients including oils, emulsifiers (surfactants), and cosolvents were used. A (pseudo)ternary phase diagram was constructed to optimize the quantitative ratio of the model component composition of the SEDDS. The selected model formulations of the SEDDS were evaluated for their emulsification ability. A series of stability tests were also conducted for the model formulations of the SEDDS, including stability at various pH levels and dilution volumes, stability under six cycles of heating to 45±0,5 °C and cooling to 4 °C, and four cycles of freezing to −20±0,5 °C and thawing.

Results. During the study, solubilization of adamantylbromophenylamine in purified water using the SEDDS approach was achieved. The composition of liquid SEDDS adamantylbromophenylamine in the form of a pre-emulsion concentrate has been developed and optimized. It was found that the liquid SESD of adamantylbromophenylamine of the final composition is resistant to various pH of the medium and dilution volumes and remains stable after six cycles of heating to 45±0.5 °C − cooling to 4±0.5 °C and four cycles of freezing to −20±0.5 °C − thawing.

Conclusions. The composition of liquid SEDDS adamantylbromophenylamine in the form of a pre-emulsion concentrate has been developed: API: adamantylbromophenylamine − 10.0 mg; BB: Cremophor® EL − 135.0 mg; Labrafac™ PG − 15.0 mg. Based on the results of the study of the emulsification ability and stability of the developed composition, it was concluded that the further development of the composition of an oral medicinal product based on SEDDS adamantylbromophenylamine is promising.

1. [Gavrilov DI, Tishkov SV, Blinskaya EV, et al. Development of approaches to the creation of self-emulsifying drug delivery systems. Farmacevticheskoe delo i tekhnologiya lekarstv = Pharmaceutical Business and Drug Technology. 2023;1:34-42 (In Russ.)]. doi: 10.33920/med-13-2301-03.

2. [Gavrilov DI, Tishkov SV, Blinskaya EV, et al. Excipients used to create self-emulsifying drug delivery systems. Farmacevticheskoe delo i tekhnologiya lekarstv = Pharmaceutical Business and Drug Technology. 2023;1:25-33 (In Russ.)]. doi: 10.33920/med-13-2301-02.

3. Bhalani DV, Nutan B, Kumar A, Singh Chandel AK. Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics. Biomedicines. 2022 Aug 23;10(9):2055. doi: 10.3390/biomedicines10092055.

4. Koli AR, Ranch KM, Patel HP, et al. Oral bioavailability improvement of felodipine using tailored microemulsion: Surface science, ex vivo and in vivo studies. Int J Pharm. 2021 Mar 1;596:120202. doi: 10.1016/j.ijpharm.2021.120202.

5. Koehl NJ, Henze LJ, Kuentz M, et al. Supersaturated Lipid-Based Formulations to Enhance the Oral Bioavailability of Venetoclax. Pharmaceutics. 2020 Jun 18;12(6):564. doi: 10.3390/pharmaceutics12060564.

6. Kesharwani R, Jaiswal P, Patel DK, et al. Lipid-Based Drug Delivery System (LBDDS): An Emerging Paradigm to Enhance Oral Bioavailability of Poorly Soluble Drugs. Biomedical Materials & Devices. 2023; 1:648-663. doi: 10.1007/s44174-022-00041-0.

7. Postina A, To D, Zöller K, Bernkop-Schnürch A. Oral peptide drug delivery: design of SEDDS providing a protective effect against intestinal membrane-bound enzymes. Drug Deliv Transl Res. 2025 Apr 24. doi: 10.1007/s13346-025-01852-6.

8. Laffleur F, Millotti G, Lagast J. An overview of oral bioavailability enhancement through self-emulsifying drug delivery systems. Expert Opin Drug Deliv. 2025 May;22(5):659-671. doi: 10.1080/17425247.2025.2479759.

9. Sandmeier M, Wong ET, Nikolajsen GN, et al. Oral formulations for cannabidiol: Improved absolute oral bioavailability of biodegradable cannabidiol self-emulsifying drug delivery systems. Colloids Surf B Biointerfaces. 2025 Nov;255:114879. doi: 10.1016/j.colsurfb.2025.114879.

10. Mohamad Sukri N, Abd Rahim N, El Enshasy HA, et al. Comparative review of translational approaches in lipid-based and water-based encapsulation strategies for coenzyme Q10. Drug Deliv Transl Res. 2026 Feb;16(2):415-438. doi: 10.1007/s13346-025-02015-3.

11. [Patent RUS № 2376986/27.12.09. Byul. №36 Seredenin SB, Pyatin BM, Avdyunina NI, Alekseev KV, Grushevskaya LN, Suldin AS. Pharmaceutical composition based on ladasten. (In Russ.)]. Доступно по: https://www.fips.ru/registers-doc-view/fips_servlet?DB=RUPAT&DocNumber=2376986&TypeFile=html. Ссылка активна на 15.05.2026.

12. [Suldin AS. Development of solid dosage forms of ladasten and a combined drug with psychotropic action. [dissertation] Perm; 2015. (In Russ.)].

13. [Morozov IS. Farmakologiya adamantanov / Morozov IS, Petrov VI, Sergeeva SA. Volgograd: Volgograd medical academy, 2001. (In Russ.)].