Formulation and evaluation of mucoadhesive buccal tablet containing peptide-fatty acid conjugate
- 주제(키워드) Mucoadhesive buccal tablets , HPMC 4000 , Non-invasive , Leuprolide-oleic acid conjugate , Leuprolide-oleic nanoparticles
- 주제(DDC) 615.1
- 발행기관 아주대학교
- 지도교수 이범진
- 발행년도 2023
- 학위수여년월 2023. 2
- 학위명 석사
- 학과 및 전공 일반대학원 약학과
- 실제URI http://www.dcollection.net/handler/ajou/000000032642
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
This study aimed to design Leuprolide as mucoadhesive buccal tablets and to manufacture and evaluate the buccal tablets containing Leuprolide-oleic acid conjugate (LOC) and self-assembled Leuprolide-oleic acid nanoparticle (LON) developed in the previous study. Hydroxypropyl methylcellulose (HPMC 4000cps) mucoadhesive polymer was used, and tablets were prepared by direct compression. The formulations were characterized by different parameters such as weight, content uniformity, thickness, hardness, swelling index, disintegration time, mucoadhesion time, and drug release studies. The chosen formulation maintained an adhesion time of up to 6.43 hours and a disintegration time of 4.10 hours. In mucoadhesive tablets, the stability of the drugs was tested in human mimic saliva (pH 6.8 PBS) for 2 hours, and it was found to be stable. Furthermore, the designed LEU formulation and the LOC and LON developed in the previous study were prepared as buccal tablets and compared and evaluated. Through in vitro dissolution (USP paddle II method) and in vitro permeation (Franz diffusion cell (DHC-6TD, Logan, USA)) studies, buccal tablets containing LON showed the highest absorption rate. Therefore, buccal tablets containing self-assembled LON can effectively increase the medication compliance of vulnerable patients (children and the elderly) by improving the bioavailability and permeation rate of Leuprolide, a poorly soluble drug.
more초록/요약
본 연구의 목적은 Leuprolide (LEU)를 점막부착성 협측 정제로 설계하고, 이전 연구에서 개발한 LEU-올레산 접합체 (LOC) 및 자기조립 LEU-올레산 나노입자 (LON)를 함유하는 협측 정제를 제조 및 평가하는 것이다. Hydroxypropyl methylcellulose (HPMC 4000cps) 점막부착성 중합체를 사용하였으며 정제는 직접 타정하여 제조하였다. 제형은 중량, 함량 균일성, 두께, 경도, 팽윤 지수, 붕해 시간, 점막접착시간 및 약물 방출 연구와 같은 다양한 매개변수에 의해 특성화되었다. 선택한 제형은 최대 6.43시간의 접착 시간과 약 4시간의 붕해 시간을 유지했다. 점막부착성 정제에서 약물의 안정성은 인간모방타액 (pH 6.8 PBS)에서 2시간 동안 시험한 결과 안정한 것으로 나타났다. 또한, 설계된 LEU 제형과 이전 연구에서 개발된 LOC 및 LON을 협측 정제로 제조하여 비교 평가하였다. 시험관내 용해 (USP 패들 II 방법) 및 시험관 내 침투(Franz 확산 셀 (DHC-6TD, Logan, USA)) 연구를 통해 LON을 함유한 협측 정제가 가장 높은 흡수율을 나탄냈다. 따라서 자가조립 LON (Leuprolide-oleic acid nanoparticle)을 포함한 협측 정제는 난용성 약물인 Leuprolide의 생체이용률 및 투과율을 개선하여 취약계층환자 (어린이 및 노인)의 복약 순응도를 높이는 효과적인 수단이 될 수 있다.
more목차
1. Introduction 1
2. Materials and Methods 6
2.1. Materials 6
2.2. Preparation of mucoadhesive buccal tablet 6
2.2.1. Preparation of LOC and LON 6
2.2.2. Manufacturing of buccal tablet 7
2.3. Evaluation of buccal tablets 9
2.3.1. Uniformity of weight, hardness, and friability 9
2.3.2. Drug content and Surface pH measurement 9
2.4. Swelling test 10
2.5. Mucoadhesive residence time 10
2.6. Disintegration study 11
2.7. In vitro, dissolution study 11
2.8. In vitro, permeation study 12
2.9. Physicochemical properties measurements of buccal tablet 13
2.9.1. Fourier transform infrared spectroscopy (FT-IR) 13
2.9.2. Differential scanning calorimetry (DSC) 13
3. Results and discussions 14
3.1. Screening of mucoadhesive polymers 14
3.2. Formulation design of buccal tablets 19
3.2.1. Evaluation of mucoadhesive buccal tablets 19
3.2.2. Dissolution and Swelling study 22
3.2.3. Mucoadhesive residence time and Disintegration test 25
3.3. In vitro, dissolution test 27
3.4. In vitro, permeation test 29
3.5. Physicochemical properties of buccal tablets 33
3.5.1. Fourier transform infrared spectroscopy (FT-IR) 33
3.5.2. Differential scanning calorimetry (DSC) 35
4. Conclusions 38
5. References 39
국문초록 43
