Purpose

Long-acting solid lipid microparticles of tetracycline hydrochloride (TH) were prepared using solvent-free twin screw hot melt dispersion technique utilizing biocompatible lipids. Design of experiments was employed to assess the formulation and process parameters followed by statistical analysis.

Methods

Plackett–Burman design generated 12 experiments containing varying ratios of lipids and TH (1:2 to 1:8). Compatibility studies by DSC were conducted on these physical mixtures of drug: lipids to check interactions and obtain an indication of lipids melting range. Microparticles were fabricated and evaluated for flow properties, particle size distribution, surface morphology, drug content, percent entrapment efficiency (PDE), and drug diffusion studies. Impact of critical process parameters on responses like throughput and specific mechanical energy consumption (SMEC) was evaluated using central composite design (CCD).

Results

DSC study confirmed compatibility of selected C16 to C18 lipids. Microscopic analysis enabled understanding changes in surface morphology pre- and post-diffusion. Lipid compositions and ratios had shown impact on drug diffusion at 2 h and 72 h. PDE was directly linked to TH: lipid ratio in the formulations. Stability of the microparticles was confirmed by assay and XRD and FTIR analysis on selected formulations.

Conclusion

Stearic acid and hydrogenated castor oil revealed significant impact on drug diffusion and micromeritic properties, respectively. Low feed rates and high screw speeds led to increase in SMEC. Morphology of melt agglomerates was controlled by varying the feed rates. Microparticles with anticipated particle size and diffusion profiles were achieved with the outlined process, which were deemed suitable to administer inside periodontal cavities.

中文翻译：

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基于双螺杆热熔分散法制备固体脂质微粒实验设计的选择性C16-C18脂质筛选及工艺优化

目的

使用无溶剂双螺杆热熔分散技术，利用生物相容性脂质制备了盐酸四环素 (TH) 的长效固体脂质微粒。采用实验设计来评估配方和工艺参数，然后进行统计分析。

方法

Plackett-Burman 设计产生了 12 个包含不同比例的脂质和 TH（1:2 到 1:8）的实验。DSC 对这些药物：脂质的物理混合物进行了相容性研究，以检查相互作用并获得脂质熔程的指示。制造微粒并评估其流动特性、粒度分布、表面形态、药物含量、包封率 (PDE) 和药物扩散研究。使用中央复合设计 (CCD) 评估关键工艺参数对吞吐量和特定机械能耗 (SMEC) 等响应的影响。

结果

DSC 研究证实了所选 C16 与 C18 脂质的相容性。显微分析能够理解扩散前后表面形态的变化。脂质成分和比例在 2 小时和 72 小时显示出对药物扩散的影响。PDE 与制剂中的 TH：脂质比直接相关。微粒的稳定性通过对选定制剂的测定以及 XRD 和 FTIR 分析得到证实。

结论

硬脂酸和氢化蓖麻油分别显示出对药物扩散和微粒特性的显着影响。低进料速度和高螺杆速度导致 SMEC 增加。通过改变进料速率来控制熔体附聚物的形态。通过概述的过程实现了具有预期粒径和扩散曲线的微粒，这些过程被认为适合在牙周腔内给药。