Salt-induced nanosuspension via acid-base neutralization for enhanced drug dissolution rate
- 주제(키워드) pH-dependent drugs , salt-induced effect , acid-base neutralization , surfactant-driven micellization , nanonization , nano-amorphousness , hydrogen bonding , enhanced dissolution
- 발행기관 아주대학교
- 지도교수 Beom-Jin Lee
- 발행년도 2020
- 학위수여년월 2020. 8
- 학위명 석사
- 학과 및 전공 일반대학원 약학과
- 실제URI http://www.dcollection.net/handler/ajou/000000030166
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
An acid-base neutralization technique generated interest for the ability to achieve an enhanced dissolution of pH-dependent weakly basic or acidic poorly water-soluble drugs. However, the underlying nanonization mechanism, following acid-base neutralization, requires further elucidation. We hypothesized that nanonization of drug particles after neutralization could be attributed to the “salt-induced effect” and surfactant-driven micellization. Rebamipide (RBM) and valsartan (VAL) were chosen as model drugs owing to poor water solubility and pH-dependent aqueous solubility. The drug nanosuspension was rapidly obtained via salt formation (NaCl) after neutralization of the drug in basic NaOH solution and poloxamer 407 (POX 407) in acidic HCl solution. The nanosuspension surrounded by NaCl salt was further stabilized by POX 407. The resulting NaCl salt modulated the critical micelle aggregation of POX 407, stabilizing the drug-loaded nanosuspension in a cage of salt and micellar surfactant. In non-assisted homogenization, size analysis indicated the relationship between salt concentration and size reduction. Fourier transform infrared (FTIR) spectra revealed that the existence of hydrogen bonding between the drug and surfactant after neutralization, attributed to nanosuspension size reduction. Changes in drug crystallinity to nano-amorphous state were confirmed by powder X-ray diffraction (PXRD). Overall, the salt-induced drug nanosuspension synergistically enhanced the dissolution rate, narrowing a gap between drug dissolution profiles in different pH environment.
more목차
1. Introduction 1
2. Materials and Methods 4
2.1. Materials 4
2.2. Methods 4
2.2.1. Preparation of neutralized nanosuspensions 4
2.2.2. Characterization of neutralized nanosuspensions 7
2.2.3. Stability analysis 7
2.2.4. Critical micelle concentration (CMC) determination 8
2.2.5. HPLC analysis 9
2.2.6. Dissolution studies 9
2.2.7. PXRD analysis 10
2.2.8. Morphological analysis 11
2.2.9. FTIR analysis 11
2.2.10. Statistical analysis 11
3. Results and Discussion 13
3.1. Effects of salt-induction on nanosuspensions after neutralization 13
3.2. CMC analysis 15
3.3. Stability of neutralized nanosuspensions 18
3.4. Effects of POX 407 concentration in neutralized nanosuspensions 20
3.5. Morphology of freeze-dried neutralized nanosuspensions 23
3.6. PXRD analysis 26
3.7. FTIR analysis 30
3.8. Dissolution studies 33
4. Conclusion 36
5. References 37
