开发复杂剂型的生物等效(BE)通用产品,如使用热熔挤出(HME)制备的皮质类固醇如地塞米松的玻璃体内植入物(IVIs),基于可生物降解的聚(丙交酯-共-乙交酯)(PLGA)聚合物,可以是具有挑战性的。更好地了解IVIs的物理化学和物理机械性能之间的关系及其对药物释放和眼部生物利用度的影响对于开发新的BE方法至关重要。有可能IVIs的关键物理化学和物理机械特性,如药物特性,植入物表面粗糙度,机械强度和韧性,植入物侵蚀可能因不同的成分而异,导致药物释放的变化。因此,这项研究调查了以下假设:使用单程热熔挤出(HME)制备的含有20%药物和80%PLGA聚合物的生物可降解眼科植入物在物理化学和/或物理机械性能以及药物释放方面存在差异,具体取决于其PLGA聚合物组成.将酸封端的PLGA与酯封端的PLGA混合以制备三种配方:HME-1,HME-2和HME-3,含有100%,80%,和60%w/w的酸封端的PLGA。Further,这项研究比较了每种组合物的独立批次之间的药物释放。体外释放试验(IVRT)表明,HME-1植入物可以通过其与HME-2和HME-3的释放曲线容易地区分,其中HME-2和HME-3的释放相似。在早期阶段,药物释放通常与聚合物组成和植入物性能密切相关,随着PLGA酸含量的增加,释放量增加(对于第1天的释放,R2=0.80)和/或升高的表面粗糙度(对于第1天和第14天的释放,R2≥0.82)。Further,植入物的机械强度和韧性与PLGA酸含量和第1天的药物释放成反比。对于每种组合物,来自独立批次的药物释放是相似的。该项目的发现可能有助于开发基于PLGA聚合物的通用眼部植入物产品。
Developing bioequivalent (BE) generic products of complex dosage forms like intravitreal
implants (IVIs) of corticosteroids such as dexamethasone prepared using hot-melt extrusion (HME), based on biodegradable poly (lactide-co-glycolide) (PLGA) polymers, can be challenging. A better understanding of the relationship between the physicochemical and physicomechanical properties of IVIs and their effect on drug release and ocular bioavailability is crucial to develop novel BE approaches. It is possible that the key physicochemical and physicomechanical properties of IVIs such as drug properties, implant surface roughness, mechanical strength and toughness, and implant erosion could vary for different compositions, resulting in changes in drug release. Therefore, this study investigated the hypothesis that biodegradable ophthalmic dexamethasone-loaded
implants with 20% drug and 80% PLGA polymer(s) prepared using single-pass hot-melt extrusion (HME) differ in physicochemical and/or physicomechanical properties and drug release depending on their PLGA polymer composition. Acid end-capped PLGA was mixed with an ester end-capped PLGA to make three formulations: HME-1, HME-2, and HME-3, containing 100%, 80%, and 60% w/w of the acid end-capped PLGA. Further, this study compared the drug release between independent batches of each composition. In vitro release tests (IVRTs) indicated that HME-1
implants can be readily distinguished by their release profiles from HME-2 and HME-3, with the release being similar for HME-2 and HME-3. In the early stages, drug release generally correlated well with polymer composition and implant properties, with the release increasing with PLGA acid content (for day-1 release, R2 = 0.80) and/or elevated surface roughness (for day-1 and day-14 release, R2 ≥ 0.82). Further, implant mechanical strength and toughness correlated inversely with PLGA acid content and day-1 drug release. Drug release from independent batches was similar for each composition. The findings of this project could be helpful for developing generic PLGA polymer-based ocular implant products.