拉米夫定(LMD),2'-脱氧-3'-硫胞苷的对映异构体,在对抗HIV-1和管理乙型肝炎病毒感染中起着至关重要的作用。尽管有效,挑战来自其难以流动和在储存过程中结块的趋势,需要在压片之前进行制粒步骤,因为直接压缩已被证明是无效的。本研究旨在使用响应面法优化拉米夫定球形团聚体,深入研究设计因素之间的复杂关系(吐温的集中,span,和丙酮)和实验结果(产量和粒度)通过中心复合材料设计。采用方差分析(ANOVA)进行优化,准乳液溶剂扩散(QESD)结晶技术用于检查点批次。这项技术,涉及单一溶剂和具有表面活性剂的反溶剂,展示了流动性的显着增强和减少的存储结块。各种表面活性剂的影响[羟丙基甲基纤维素(HPMC),聚山梨酯80和山梨糖醇单油酸酯]在颗粒形态上,流动性,彻底评估结晶过程中的储存团聚。在实现直接压制成片剂的同时,LMD团聚体的多孔结构对压片机生产速度提出了挑战,提示调整,如降低冲头速度或实施预压缩步骤。与直接压缩和湿法制粒方法相比,崩解和体外药物释放取得了积极成果。总之,QESD结晶技术成功地产生了空心,具有增强性能的球形LMD团聚体,代表药物制剂的重要里程碑。
Lamivudine (LMD), an enantiomer of 2\'-deoxy-3\'-thiacytidine, plays a crucial role in combatting HIV-1 and managing hepatitis B virus infections. Despite its effectiveness, challenges arise from its difficult flowability and tendency to agglomerate during storage, necessitating a granulation step before tablet compression, as direct compression has proven ineffective. This
study aimed to optimize Lamivudine spherical agglomerates using response surface methodology, delving into the intricate relationship between design factors (concentration of tween, span, and acetone) and experimental outcomes (yield and particle size) through central composite design. Analysis of variance (ANOVA) was employed for optimization, with the Quasi-emulsion solvent-diffusion (QESD) crystallization technique utilized for the checkpoint batch. This technique, involving a single solvent and antisolvent with surfactants, showcased remarkable enhancements in flowability and reduced storage agglomeration. The impact of various surfactants [Hydroxy Propyl Methyl Cellulose (HPMC), polysorbate 80, and sorbitane monooleate] on particle morphology, flowability, and storage agglomeration during crystallization was thoroughly assessed. While achieving direct compression into tablets, the porous structure of LMD agglomerates presented challenges in tablet press production speeds, prompting adjustments such as reducing punch speed or implementing a precompression step. Positive outcomes were realized for disintegration and in vitro drug release in comparison to direct compression and wet granulation methods. In conclusion, the QESD crystallization technique successfully yielded hollow, spherical LMD agglomerates with enhanced properties, representing a significant milestone in pharmaceutical formulation.