Abdelkader Hamdy, Abdallah Ossama Y, Salem Hesham, Alani Adam W G, Alany Raid G
Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt.
J Pharm Pharmacol. 2014 Oct;66(10):1439-50. doi: 10.1111/jphp.12277. Epub 2014 Jun 19.
The solid-state interactions of fused mixtures nimesulide (ND) with polyethylene glycol (PEG) 4000, urea or mannitol were studied through constructing thaw-melt phase equilibrium diagrams.
The solid-state characteristics were investigated using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Various types of interactions were identified such as the formation of a eutectic system of ND-PEG 4000, monotectic system of ND-urea and complete solid immiscibility of ND with mannitol. The effects of carrier concentrations on the equilibrium solubility and in-vitro dissolution characteristics were studied.
Linear increases (R(2) > 0.99) in the aqueous solubility of ND in various concentrations of PEG 4000 and urea were obtained, whereas mannitol did not exhibit any effect on the solubility of ND. Similar trends were obtained with the dissolution efficiency of the fused mixtures of ND with PEG 4000 and urea compared with the corresponding physical mixtures and untreated drug. The analgesic effects of untreated ND and the selected formulations were investigated by evaluating the drug's ability to inhibit the acetic acid-induced writhing response.
The analgesic effect of ND in a eutectic mixture with PEG 4000 and a monotectic mixture with urea was potentiated by 3.2 and 2.7-fold respectively compared with the untreated drug.
通过构建冻融相平衡图，研究尼美舒利（ND）与聚乙二醇（PEG）4000、尿素或甘露醇的熔融混合物的固态相互作用。
采用差示扫描量热法（DSC）和X射线衍射法（XRD）研究固态特性。确定了各种类型的相互作用，如ND-PEG 4000共晶体系的形成、ND-尿素偏晶体系的形成以及ND与甘露醇的完全固溶不混溶。研究了载体浓度对平衡溶解度和体外溶出特性的影响。
ND在不同浓度的PEG 4000和尿素中的水溶性呈线性增加（R²＞0.99），而甘露醇对ND的溶解度没有任何影响。与相应的物理混合物和未处理药物相比，ND与PEG 4000和尿素的熔融混合物的溶出效率也呈现类似趋势。通过评估药物抑制醋酸诱导的扭体反应的能力，研究了未处理的ND和所选制剂的镇痛效果。
与未处理药物相比，ND与PEG 4000的共晶混合物和与尿素的偏晶混合物的镇痛效果分别增强了3.2倍和2.7倍。
