Exploration of Conventional and FDM-Mediated 3D Printed Tablets Fabricated Using HME-Based Filaments for pH-Dependent Drug Delivery

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech Pub Date : 2025-03-27 DOI:10.1208/s12249-025-03088-6

Ruchira Patil, Prajakta Bule, Naveen Chella

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Abstract

Hot melt extrusion (HME) helps to improve the solubility of BCS class II and IV molecules. The downstream processing of the resulting filaments was crucial in developing the final dosage form. The present work investigates advantages of combining HME with fused deposition modelling (FDM) 3-Dimensional (3D) printing in delivering the naringenin to the colon to treat inflammatory bowel disease. HME filaments were made using a pH-sensitive polymer hydroxypropyl methylcellulose acetate succinate for the localized delivery of naringenin at the colonic pH. Polyethylene glycol (PEG – 4000) and Aerosil 200 were incorporated as plasticizer and flow modulator respectively, to facilitate the extrusion process. Naringenin was converted to amorphous form as confirmed by differential scanning calorimetry and powder x-ray diffraction. The optimized filament showed 0.03, 11.52 and 77.80% drug release at pH 1.2, 6.8 and 7.4 respectively. The tablets produced with the optimized filament by compression and 3D printing also confirmed the presence of naringenin in amorphous form and demonstrated pH-dependent release followed by zero-order release independent of the concentration. The dissolution profiles of FDM 3D printed (3DP) tablets with varying dimensions and infill densities suggested that both significantly influenced drug release from the tablets without altering the composition of tablets, indicating the potential application of 3D printing technology in developing personalized medicine according to patient requirements. These promising results may be valuable in evaluating the potential of naringenin in animal models, which may further facilitate clinical applications.

Graphical Abstract

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利用HME-Based细丝制备用于ph依赖性药物递送的传统和fdm介导的3D打印片剂的探索

热熔挤压（HME）有助于提高BCS II类和IV类分子的溶解度。产生的细丝的下游加工在开发最终剂型中至关重要。本研究探讨了将HME与熔融沉积建模（FDM）三维（3D）打印相结合，将柚皮素输送到结肠治疗炎症性肠病的优势。采用ph敏感聚合物羟丙基甲基纤维素乙酸琥珀酸酯制备HME细丝，用于在结肠ph下局部递送柚皮素。聚乙二醇（PEG - 4000）和Aerosil 200分别作为增塑剂和流量调节剂，以促进挤出过程。通过差示扫描量热法和粉末x射线衍射证实柚皮素转化为无定形。在pH值为1.2、6.8和7.4时，该纤维的释药率分别为0.03%、11.52%和77.80%。通过压缩和3D打印制备的柚皮素片也证实了柚皮素的无定形存在，并表现出ph依赖性释放，其次是与浓度无关的零级释放。不同尺寸和填充密度的FDM 3D打印（3DP）片剂的溶出曲线表明，在不改变片剂成分的情况下，两者都会显著影响片剂的药物释放，这表明3D打印技术在根据患者需求开发个性化药物方面具有潜在的应用前景。这些结果对评价柚皮素在动物模型中的应用潜力具有一定的参考价值，为柚皮素的临床应用提供参考。图形抽象

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来源期刊

AAPS PharmSciTech 医学-药学

CiteScore

6.80

自引率

3.00%

发文量

264

审稿时长

2.4 months

期刊介绍： AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.