Introduction

Oral dispersible tablets (ODTs) are promising pharmaceutical dosage forms and, theoretically, could be used for many active pharmaceutical ingredients. The development of ODTs by direct compression with rapid disintegration and suitable hardness is a formulation challenge. The hypothesis of the present work is to prepare a single super-disintegrant multifunctional excipient for the production of ODTs.

Method

A single multifunctional tablet component was prepared by crosslinking of chitosan-hydrochloride (CS-H) using multivalent anionic salts, such as carbonate, phosphate, and sulfate. An optimized tablet characteristic concerning the disintegration time (DT) and the compaction properties is obtained utilizing the response surface methodology (RSM). The DT and elastic ratio (ER) were used as responses, and two other factors were studied, i.e., concentration of anions (C_sa) and compression pressure (P_c). The obtained crosslinked chitosan anionic salt powders were also characterized in terms of chemical interaction, flowability, moisture uptake, water sorption, and release behavior of an incorporated chemically reactive model drug (ibuprofen lysinate).

Results

Based on RSM, the optimal concentrations of chitosan phosphate and chitosan sulfate (as %) were 61.14, 60.89, and 64.65, respectively. The optimal compression pressures (in Mpa) of chitosan carbonate, phosphate, and sulfate were 107.02, 110.39, and 100, respectively. Moreover, 0.31, 0.15, and 0.47 (predicted elastic ratio) and 8, 17, and 2 (disintegration time, s) were obtained for chitosan carbonate, phosphate, and sulfate, respectively. The infrared spectroscopy and the differential scanning microscopy studies were used as tools to detect the interaction. Mean dissolution time was 20.5 min for chitosan hydrochloride compared with 6.9–8.52 for chitosan anionic salts, while the dissolution efficiency was 0.54 for chitosan compared with > 0.8 for chitosan anionic salts. Drug release was higher from chitosan anionic salt matrix systems compared with that of chitosan hydrochloride tablets.

Conclusion

The RSM was successfully utilized to prepare optimized tablets using chitosan anionic salt as a single oral dispersible tablet excipient. These salts exhibited suitable physico-mechanical properties upon compaction with a concomitant super-disintegration ability. The chemical reactivity of chitosan hydrochloride against negatively charged molecules was dependent upon crosslinking with negatively charged anions as indicated by the release behavior of ibuprofen lysinate from the chitosan anionic salt matrix systems.

中文翻译：

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口腔分散性壳聚糖阴离子盐片的设计，制备与评价

介绍

口服分散片（ODT）是有前途的药物剂型，理论上可用于许多活性药物成分。通过直接压缩，快速崩解和合适的硬度来开发ODT是一项配方挑战。本工作的假设是制备用于生产ODT的单一超崩解多功能赋形剂。

方法

通过使用多价阴离子盐，例如碳酸盐，磷酸盐和硫酸盐交联壳聚糖盐酸盐（CS-H），制备了单一的多功能片剂组分。利用响应表面方法（RSM）获得了有关崩解时间（DT）和压实特性的优化片剂特性。使用DT和弹性比（ER）作为响应，并研究了另外两个因素，即阴离子浓度（C _sa）和压缩压力（P _c）。所得交联的壳聚糖阴离子盐粉末的特征还在于掺入的化学反应性模型药物（布洛芬赖氨酸盐）的化学相互作用，流动性，水分吸收，吸水率和释放行为。

结果

基于RSM，磷酸壳聚糖和硫酸壳聚糖的最佳浓度（以％计）分别为61.14、60.89和64.65。壳聚糖的碳酸盐，磷酸盐和硫酸盐的最佳压缩压力（单位为Mpa）分别为107.02、110.39和100。另外，壳聚糖碳酸酯，磷酸盐和硫酸盐分别获得0.31、0.15和0.47（预测的弹性比）和8、17和2（崩解时间，s）。红外光谱和差示扫描显微镜研究被用作检测相互作用的工具。壳聚糖盐酸盐的平均溶解时间为20.5分钟，而壳聚糖阴离子盐的平均溶解时间为6.9–8.52，而壳聚糖的溶解效率为0.54，而壳聚糖阴离子盐的平均溶解时间为> 0.8。

结论

使用壳聚糖阴离子盐作为单一的口服分散片剂赋形剂，成功地利用RSM制备了优化的片剂。这些盐在压实时表现出合适的物理机械性能，同时具有超崩解能力。壳聚糖盐酸盐对带负电荷的分子的化学反应性取决于与带负电荷的阴离子的交联，如布洛芬赖氨酸盐从壳聚糖阴离子盐基质体系中的释放行为所表明。