Abdeltawab Hani, Svirskis Darren, Hill Andrew G, Sharma Manisha
School of Pharmacy, Faculty of Medical & Health Sciences, The University of Auckland, Auckland 1023, New Zealand.
Department of Surgery, South Auckland Clinical Campus, The University of Auckland, Middlemore Hospital, Auckland 2025, New Zealand.
Gels. 2022 Aug 2;8(8):484. doi: 10.3390/gels8080484.
Various strategies have been applied to reduce the initial burst of drug release and sustain release from poloxamer-based thermoresponsive gels. This work focussed on investigating different formulation approaches to minimise the initial burst of release and sustain the release of the small hydrophilic drug bupivacaine hydrochloride from poloxamer-based thermoresponsive gels. Various in situ gel formulations were prepared by varying the polypropylene oxide (PPO)/polyethylene oxide (PEO) ratio and by adding additives previously described in the literature. It was observed that increasing the PPO/PEO ratio from 0.28 to 0.30 reduced the initial burst release from 17.3% ± 1.8 to 9.1% ± 1.2 during the first six hours and extended the release profile from 10 to 14 days. Notably, the inclusion of sodium chloride (NaCl 0.4% /) further reduced the initial burst release to 1.8% ± 1.1 over the first 6 h. Meanwhile, physical blending with additive polymers had a negligible effect on the burst release and overall release profile. The findings suggest that extended release of bupivacaine hydrochloride, with reduced initial burst release, can be achieved simply by increasing the PPO/PEO ratio and the inclusion of NaCl.
已经应用了各种策略来减少基于泊洛沙姆的热响应凝胶的药物初始释放突释并维持其释放。这项工作着重于研究不同的制剂方法，以最小化基于泊洛沙姆的热响应凝胶中小的亲水性药物盐酸布比卡因的初始释放突释并维持其释放。通过改变聚环氧丙烷（PPO）/聚环氧乙烷（PEO）的比例并添加文献中先前描述的添加剂，制备了各种原位凝胶制剂。观察到，将PPO/PEO比例从0.28增加到0.30，在前六个小时内将初始突释从17.3%±1.8降低到9.1%±1.2，并将释放曲线从10天延长到14天。值得注意的是，加入氯化钠（0.4%NaCl）在前6小时内进一步将初始突释降低到1.8%±1.1。同时，与添加剂聚合物的物理混合对突释和整体释放曲线的影响可忽略不计。这些发现表明，通过增加PPO/PEO比例和加入NaCl，可以实现盐酸布比卡因的缓释，同时减少初始突释。
