Barghi Leila, Vekalati Afshin, Jahangiri Azin
Department of Pharmaceutics, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.
School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.
Adv Pharmacol Pharm Sci. 2023 May 11;2023:2641153. doi: 10.1155/2023/2641153. eCollection 2023.
Limited aqueous solubility and subsequent poor absorption and low bioavailability are the main challenges in oral drug delivery. Solid dispersion is a widely used formulation strategy to overcome this problem. Despite their efficiency, drug crystallization tendency and poor physical stability limited their commercial use. To overcome this defect, ternary solid dispersions of glyburide: sodium lauryl sulfate (SLS) and polyethylene glycol 4000 (PEG), were developed using the fusion (F) and solvent evaporation (SE) techniques and subsequently evaluated and compared.
Physicochemical and dissolution properties of the prepared ternary solid dispersions were evaluated using differential scanning calorimetry (DSC), infrared spectroscopy (FTIR), and dissolution test. Flow properties were also assessed using Carr's index and Hausner's ratio. The physical stability of the formulations was evaluated initially and after 12 months by comparing dissolution properties.
Formulations prepared by both methods similarly showed significant improvements in dissolution efficiency and mean dissolution time compared to the pure drug. However, formulations that were prepared by SE showed a greater dissolution rate during the initial phase of dissolution. Also, after a 12-month follow-up, no significant change was observed in the mentioned parameters. The results of the infrared spectroscopy indicated that there was no chemical interaction between the drug and the polymer. The absence of endotherms related to the pure drug from thermograms of the prepared formulations could be indicative of reduced crystallinity or the gradual dissolving of the drug in the molten polymer. Moreover, formulations prepared by the SE technique revealed superior flowability and compressibility in comparison with the pure drug and physical mixture (ANOVA, < 0.05).
Efficient ternary solid dispersions of glyburide were successfully prepared by F and SE methods. Solid dispersions prepared by SE, in addition to increasing the dissolution properties and the possibility of improving the bioavailability of the drug, showed acceptable long-term physical stability with remarkably improved flowability and compressibility features.
水溶解度有限以及随之而来的吸收不佳和生物利用度低是口服药物递送中的主要挑战。固体分散体是一种广泛使用的制剂策略，用于克服这一问题。尽管它们效率高，但药物结晶倾向和较差的物理稳定性限制了它们的商业应用。为了克服这一缺陷，采用熔融法（F）和溶剂蒸发法（SE）制备了格列本脲与十二烷基硫酸钠（SLS）和聚乙二醇4000（PEG）的三元固体分散体，随后进行了评估和比较。
采用差示扫描量热法（DSC）、红外光谱法（FTIR）和溶出度试验对制备的三元固体分散体的物理化学和溶出性质进行评估。还使用卡尔指数和豪斯纳比评估流动性。通过比较溶出性质，在初始阶段和12个月后对制剂的物理稳定性进行评估。
与纯药物相比，两种方法制备的制剂在溶出效率和平均溶出时间方面均有显著改善。然而，SE法制备的制剂在溶出初始阶段显示出更高的溶出速率。此外，经过12个月的随访，上述参数未观察到显著变化。红外光谱结果表明药物与聚合物之间没有化学相互作用。制备的制剂热重图中没有与纯药物相关的吸热峰，这可能表明结晶度降低或药物在熔融聚合物中逐渐溶解。此外，与纯药物和物理混合物相比，SE技术制备的制剂显示出更好的流动性和可压缩性（方差分析，P < 0.05）。
通过F法和SE法成功制备了高效的格列本脲三元固体分散体。SE法制备的固体分散体除了提高溶出性质和改善药物生物利用度的可能性外，还显示出可接受的长期物理稳定性，其流动性和可压缩性特征有显著改善。
