Department of Pharmaceutical Technology, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey; Department of Pharmaceutical Technology, Faculty of Pharmacy, İzmir Kâtip Çelebi University, 35620 İzmir, Turkey.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey.
Int J Pharm. 2021 Mar 1;596:120222. doi: 10.1016/j.ijpharm.2021.120222. Epub 2021 Jan 21.
Fused deposition modeling (FDM)-3D printing enables the manufacturing of dosage forms with personalized doses and controllable release profiles. Parkinson's disease is a neurodegenerative disorder that causes motor complications. In the treatment of the disease, the nonergot dopamine receptor agonist pramipexole is used in gradually increasing doses depending on patient's needs. Hence, there are various dosed commercial products of pramipexole and it is a suitable model drug for the preparation of personalized-dose 3D printed dosage forms. In this study, we prepared extended release 3D tablets of pramipexole for once daily use in Parkinson's disease. Herein, 12 different 3D tablet formulations were prepared and in vitro characterizations were performed on these formulations. The formulations were compared with the marketed tablet and the optimum formulation was selected. The chosen formulation was prepared with commercially available doses of pramipexole and also with intermediate doses which are not available in the market to demonstrate the applicability of 3D printing in personalized dosing. Stability studies, which have innovative features for 3D tablets, were conducted in optimum 3D tablet formulation for 6 months at 25 °C/60% relative humidity (RH) and 40 °C/75% RH conditions. After oral administration of the optimum 3D tablets and the marketed tablets (in the same dose) to the rats, 24-hour plasma profiles were obtained and pharmacokinetic parameters were calculated. 3D tablets were successfully prepared in personalized doses and their properties were similar for almost all doses. The optimum 3D tablet formulation was found to be stable during the stability tests. 3D tablet and marketed tablet performed similar plasma profiles. The relative bioavailability of 3D tablet formulation was calculated as 107.6% compared with the marketed tablet. Briefly, in vitro and in vivo evaluations demonstrated that FDM-3D printing is a promising technology for the development of personalized dosage forms with extended release property and comparable to conventional ones.
熔融沉积成型（FDM）-3D 打印可制造具有个性化剂量和可控释放特征的剂型。帕金森病是一种神经退行性疾病，会导致运动并发症。在该疾病的治疗中，非麦角多巴胺受体激动剂普拉克索逐渐增加剂量，具体取决于患者的需求。因此，有各种剂量的普拉克索商业产品，它是制备个性化剂量 3D 打印剂型的合适模型药物。在这项研究中，我们制备了用于帕金森病每日一次给药的普拉克索延长释放 3D 片剂。在此，制备了 12 种不同的 3D 片剂配方并对这些配方进行了体外特征研究。将这些配方与市售片剂进行比较并选择最佳配方。选择的配方使用市售剂量的普拉克索和市场上没有的中间剂量制备，以证明 3D 打印在个性化给药中的适用性。在 25°C/60%相对湿度（RH）和 40°C/75%RH 条件下，对最佳 3D 片剂配方进行了 6 个月的稳定性研究，该研究对 3D 片剂具有创新性。将最佳 3D 片剂和市售片剂（相同剂量）给大鼠口服后，获得了 24 小时的血浆谱并计算了药代动力学参数。成功制备了个性化剂量的 3D 片剂，几乎所有剂量的片剂性质都相似。在稳定性测试中，发现最佳 3D 片剂配方稳定。3D 片剂和市售片剂的血浆谱相似。与市售片剂相比，3D 片剂配方的相对生物利用度计算为 107.6%。简而言之，体外和体内评价表明，FDM-3D 打印是开发具有延长释放特性和与传统制剂相当的个性化剂型的有前途的技术。
