Purpose

Iloperidone (Ilo) is an antipsychotic drug having low and pH-dependent solubility, hence less bioavailability. Thus, the aim of this study was to prepare and characterize binary (TAPOL B) and ternary complexes (TAPOL T) of drug with Kolliphor P-188 and tartaric acid to improve solubility. Further, sublingual tablets incorporating ternary complex were formulated to improve the dissolution.

Methods

Preliminary screening studies were conducted to select the acidifying agent and polymer based on saturation solubility studies. Binary and ternary complexes were prepared by the melting method. Complexes were characterized by DSC, powder X-ray diffraction (PXRD), FTIR, microenvironmental studies, and in vitro dissolution studies. The sublingual tablets of ternary complexes were prepared by the direct compression method and evaluated for weight variation, disintegration time, and dissolution studies.

Results

Based on solubility studies, Kolliphor P-188 and tartaric acid were selected as polymer and acidifying agents. DSC studies and FTIR spectra showed the interaction of drugs with polymer and acidifying agents. PXRD spectra showed the crystalline nature of complexes. Microenvironmental studies carried out in pH 6.8 showed a drastic decrease in pH with ternary complex as compared with binary complex. Dissolution studies showed an increase in dissolution, TAPOL T > TAPOL B > drug. The sublingual tablets showed disintegration time < 30 s and more than 80% of a drug released within 10 min. Due to the presence of tartaric acid and polymer, solubility of the drug increases tremendously.

Conclusion

The present study demonstrates the increase in solubility and release of Iloperidone due to the microenvironmental pH effect from sublingual tablets. Hence, microenvironmental pH modification is a good approach to increase drug solubility and dissolution.

中文翻译：

---

微环境pH调节法制备的伊潘立酮舌下片的制备与表征

目的

伊潘立酮（Ilo）是一种抗精神病药，具有低溶解度和pH依赖性，因此生物利用度较低。因此，本研究的目的是制备和表征药物与Kolliphor P-188和酒石酸的二元（TAPOL B）和三元复合物（TAPOL T），以提高溶解度。此外，配制掺有三元复合物的舌下片剂以改善溶解。

方法

根据饱和溶解度研究进行了初步筛选研究，以选择酸化剂和聚合物。通过熔融方法制备二元和三元络合物。通过DSC，粉末X射线衍射（PXRD），FTIR，微环境研究和体外溶出研究来表征复合物。通过直接压片法制备三元复合物的舌下片剂，并评估其重量变化，崩解时间和溶出度研究。

结果

根据溶解度研究，选择Kolliphor P-188和酒石酸作为聚合物和酸化剂。DSC研究和FTIR光谱显示药物与聚合物和酸化剂的相互作用。PXRD光谱显示了配合物的结晶性质。在pH 6.8下进行的微环境研究表明，与二元复合物相比，三元复合物的pH值急剧降低。溶出度研究显示溶出度增加，TAPOL T> TAPOL B>药物。舌下片剂显示崩解时间＜30 s，在10分钟内释放出80％以上的药物。由于酒石酸和聚合物的存在，药物的溶解度大大增加。

结论

本研究表明，由于舌下片剂的微环境pH效应，伊潘立酮的溶解度和释放增加。因此，微环境pH调节是增加药物溶解度和溶解度的好方法。