Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, New York 11439.
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, New York 11439.
J Pharm Sci. 2020 Apr;109(4):1558-1572. doi: 10.1016/j.xphs.2020.01.015. Epub 2020 Jan 29.
In this study, the processability of polyvinyl alcohol (PVA), a water-soluble polymer, into melt-extruded filaments and then into 3D printed tablets by fused deposition modeling was studied. PVA is semicrystalline with Tg and m.p. of ~45°C and ~190°C, respectively. After screening several plasticizers, sorbitol was selected to enhance melt extrudability of PVA. Carvedilol and haloperidol, 2 basic compounds with pH-dependent solubility, were used as model drugs. Miscibility of the drugs with PVA, with and without added sorbitol as plasticizer, was also tested to determine whether any amorphous solid dispersion was formed that would facilitate rapid and pH-independent dissolution. Finally, the drug release from physical mixtures, crushed extrudates, and printed tablets were determined. Owing to high m.p. and high melt viscosity of PVA, filaments containing 10% and 20% drug required 180°C-190°C for extrusion, which could be reduced to ~150°C by adding 10% sorbitol. The printing temperature of 210°C was, however, required. Miscibility of carvedilol and haloperidol with PVA were, respectively, ~20% and <10%. PVA provided complete drug release from 3D printed tablets with 10% and 20% carvedilol and 60% infill in ~45 min at both pH 2 and 6.8. However, despite relatively rapid dissolution rate, high processing temperature and limited drug-polymer miscibility could be potential development issues with PVA.
在这项研究中，研究了水溶性聚合物聚乙烯醇（PVA）的可加工性，将其熔融挤出成纤维，然后通过熔融沉积建模 3D 打印成片剂。PVA 是半结晶的，Tg 和 m.p. 分别约为 45°C 和 190°C。在筛选了几种增塑剂后，选择山梨糖醇来提高 PVA 的可熔融挤出性。卡维地洛和氟哌啶醇是两种具有 pH 依赖性溶解度的碱性化合物，被用作模型药物。还测试了药物与 PVA 的混溶性，有无添加山梨糖醇作为增塑剂，以确定是否形成任何无定形固体分散体，从而促进快速和 pH 独立的溶解。最后，测定了物理混合物、挤出物粉碎物和打印片剂的药物释放。由于 PVA 的高熔点和高熔体粘度，含有 10%和 20%药物的纤维需要 180°C-190°C 才能挤出，而添加 10%山梨糖醇可将挤出温度降低至约 150°C。然而，需要 210°C 的打印温度。卡维地洛和氟哌啶醇与 PVA 的混溶性分别约为 20%和 <10%。PVA 提供了 10%和 20%卡维地洛和 60%填充率的 3D 打印片剂的完全药物释放，在 pH 2 和 6.8 下约 45 分钟内完全释放药物。然而，尽管具有相对较快的溶解速率，但高加工温度和有限的药物-聚合物混溶性可能是 PVA 的潜在发展问题。
