Centkowska Katarzyna, Ławrecka Elżbieta, Sznitowska Malgorzata
Department of Pharmaceutical Technology, Medical University of Gdansk, Hallera Str. 107, 80-416 Gdansk, Poland.
Pharmaceutics. 2020 Mar 10;12(3):250. doi: 10.3390/pharmaceutics12030250.
The production of orodispersible films (ODFs) with suspended insoluble drug substances is still a challenge, mainly due to the difficulty associated with achieving a proper homogeneity and mechanical properties of the films. Hypromellose (HPMC) and a mixture of polyvinyl alcohol (AP) and povidone (PVP) were compared in terms of their suitability for ODFs incorporating suspended micronized loratadine (LO) in a concentration range of 10%-40%. In a planetary mixer (Thinky), a uniform dispersion of LO in an aqueous viscous casting solution was obtained. The suspended LO particles caused dose-dependent changes in the viscosity of the casting mass and affected the mechanical quality of ODFs. Drug concentrations higher than 30% reduced the film flexibility and tear resistance, depending on the polymer type. LO films with a thickness of 100 µm disintegrated within 60-100 s, with no significant influence of the LO content in the range 10%-30%. HPMC films, regardless of the drug concentration, met the pharmacopoeial requirements regarding the uniformity of the drug content. AP/PVP films were too elastic, and the drug content uniformity was not achieved. The conclusion is that, using an HPMC matrix, it is possible to obtain a high load of a poorly water-soluble drug (30% of dry film mass corresponds to a dose of 5 mg per 1.5 cm) in ODFs characterized by proper physical characteristics.
制备含有悬浮不溶性药物的口腔崩解片（ODF）仍然是一项挑战，主要是因为难以实现片剂的适当均匀性和机械性能。比较了羟丙甲纤维素（HPMC）以及聚乙烯醇（AP）和聚维酮（PVP）的混合物用于制备含10%-40%浓度范围的悬浮微粉化氯雷他定（LO）的ODF的适用性。在行星式搅拌机（Thinky）中，LO在水性粘性浇铸溶液中获得了均匀分散。悬浮的LO颗粒导致浇铸物料的粘度发生剂量依赖性变化，并影响ODF的机械质量。高于30%的药物浓度会降低薄膜的柔韧性和抗撕裂性，这取决于聚合物类型。厚度为100 µm的LO薄膜在60-100秒内崩解，10%-30%范围内的LO含量对此没有显著影响。无论药物浓度如何，HPMC薄膜均符合药典关于药物含量均匀性的要求。AP/PVP薄膜弹性过大，未实现药物含量均匀性。结论是，使用HPMC基质，可以在具有适当物理特性的ODF中获得高负载的难溶性药物（干膜质量的30%相当于每1.5 cm 5 mg的剂量）。
