Preparation and evaluation of taste-masked dextromethorphan oral disintegrating tablet

This study was aimed at preparing and evaluating oral disintegrating tablets (ODTs) using a strongly cationic resin, Amberlite(?) IRP-69, to mask the bitter taste of a delivered drug, i..e. dextromethorphan hydrobromide. The drug was loaded into the resin (referred to as resinate) or physically mixed with the resin (referred to as physical mixture), and was then incorporated into ODTs by direct compression. A variety of formulae was developed to acquire the optimal formulations of taste-masked ODTs that had acceptable hardness and mouth feel (grittiness). The optimized ODTs were further evaluated for thickness, diameter, weight, friability, disintegration time, wetting time, wetting rate, drug content, drug release and degree of bitter taste, respectively. The thickness, diameter, weight and friability of the tablet with resinate were slightly higher than those with physical mixture. The tablet with resinate had a longer disintegration time, corresponding with its slower wetting time and rate. Both tablets with resinate and physical mixture provided a sustained pattern of drug release. However, only tablets with resinate successfully masked the bitter taste of the drug. In conclusion, the combination of drug and ion exchange resin as resinate could increase the palatability and acceptability of ODTs containing bitter drugs.     

积分脉冲安培检测-高效阴离子交换色谱法测定盐酸氨基葡萄糖口腔崩解片含量

目的建立测定盐酸氨基葡萄糖口腔崩解片含量的方法。方法采用积分脉冲安培检测-高效阴离子交换色谱法测定盐酸氨基葡萄糖,优化了淋洗条件和积分脉冲安培检测条件。结果盐酸氨基葡萄糖的检测限为0.05 ng,线性范围为0.1~40μg/mL,盐酸氨基葡萄糖口腔崩解片的加样回收率为100.1%,RSD为1.17%(n=9)。结论此法可简单、快速、灵敏、准确地测定盐酸氨基葡萄糖口腔崩解片的含量。     

头孢克肟掩味口腔崩解片的研制与质量评价

目的 将头孢克肟包合于β-环糊精（HP-β-CD）中掩盖其不良气味,采取直接压片将其制成口腔崩解片加快药物的溶出,提高生物利用度。方法 以物理混合法及研磨法,制备头孢克肟原料药和HP-β-CD比例为1∶1、1∶2、1∶3的包合物,HPLC法检测包合物中头孢克肟质量分数和溶出度,结合口味测试,筛选包合物的制备方法及比例;采用Box-Behnken设计（BBD）以崩解时限和硬度为考察指标优化头孢克肟口腔崩解片（简称自制片）的处方;通过粉末流动性评价、含量测定、体外药物溶出度验证等进行最佳处方工艺验证;考察自制片、参比制剂（头孢克肟片）在Beagle犬中的药动学;考察自制片在（40.0±2.0）℃、（75±5）%恒温恒湿箱中储存3个月的稳定性。结果 当采用研磨法、头孢克肟与β-环糊精比例为1∶3时,矫味作用、药物含量、体外药物溶出度结果最好。最优处方为：含头孢克肟200 mg的包合物、交联聚维酮38.81 mg、微晶纤维素75.77 mg、甘露醇63.57 mg、乳糖15.35 mg、滑石粉2 mg、硬脂酸镁2.5 mg、微粉硅胶1.5 mg、草莓香精0.5 mg。自制片的混粉流动性良好,崩解速度快,硬度为（52.37±0.51） N、机械强度良好;含量＞98.93%;不同介质中自制片与参比制剂溶出曲线具有相似性,且自制片的累积溶出率更高。自制片生物利用度为参比制剂的110.08%;自制片的达峰浓度（C_max）为3.158 mg·L^-1,参比制剂C_max为2.982 mg·L^-1;自制片的达峰时间（t_max）为2.5 h,参比制剂t_max为2.667 h;在6.0、8.0、10.0 h,自制片的血药浓度较参比制剂显著升高（P＜0.05）。在储存过程中,自制片外观性状、含量、体外药物溶出度无显著变化。结论 制备的头孢克肟掩味口腔崩解片工艺稳定、粉末流动性良好、机械强度良好、崩解速度快、口感好、服用方便、生物利用度高、能更快发挥药效,同时稳定性良好。     

酮洛芬肠溶口腔崩解片的处方优化

目的优化酮洛芬肠溶口腔崩解片的处方,考察不同压片力和不同微晶纤维素与甘露醇比例对空白崩解片孔隙率、抗张强度和崩解时限的影响。方法采用乳化溶剂扩散法制备酮洛芬肠溶微球;以微球为原料,采用粉末直接压片法制备口腔崩解片。用Statistica统计软件对处方组成进行优化,确定微晶纤维素与甘露醇的比例。结果微晶纤维素用量一定时,随压片力的增大,空白崩解片的孔隙率减小,抗张强度增大,崩解时限延长;压片力一定时,随微晶纤维素用量的增加,空白崩解片的孔隙率和抗张强度增大,崩解时限延长;根据处方优化的结果,选择微晶纤维素与甘露醇质量比为3∶1。当片剂中加入质量分数为8%的PVPP作为崩解剂时,空白崩解片的抗张强度略微增加,崩解时限显著缩短。结论根据优化后的处方,采用粉末直接压片法制备的酮洛芬肠溶口腔崩解片符合设计要求。     

Orally disintegrating tablet of novel salt of antiepileptic drug: Formulation strategy and evaluation

The aim of present research was to design and evaluate orally disintegrating tablet (ODT) of novel lamotrigine-cyclamate salt. Box–Behnken response surface methodology was selected to design the optimized formulation. The independent factors selected were tablet hardness (X₁), disintegrant (X₂) and lubricant (X₃) levels, and responses chosen were disintegration time (DT, Y₁), friability (Y₂), T₅₀ (Y₃), and T₉₀ (Y₄). The tablets were also characterized for drug uniformity by near infrared chemical imaging (NIR-CI) and taste masking evaluation by electronic tongue. All the selected independent variables were statistically (p < 0.05) effect the Y₁ while Y₂, Y₃, and Y₄ affected only by X₂. The optimized ODT was found to meet the regulatory requirement of DT and friability specification. The NIR-CI images indicated uniform distribution of active and inactive ingredients within the tablets. The electronic tongue results were analyzed by principle component analysis (PCA). It indicated that novel salt of lamotrigine and its ODT formulation have a taste similar to cyclamic acid which is indicated by close proximity on PCA score plot, lower Euclidean distance, and high discrimination index values. Furthermore, these parameters were very close to ODT placebo formulation. On the other hand, lamotrigine, its ODT, and placebo formulation were far from each other. In summary, lamotrigine salt provides another avenue for pediatric friendly formulation for children and will enhance patience compliance.     

布洛芬口腔崩解片的研制

目的制备布洛芬口腔崩解片。方法采用正交设计考察了十二烷基硫酸钠、微晶纤维素、羧甲基淀粉钠及枸橼酸对布洛芬口腔崩解片崩解时间的影响,筛选并优化了处方和工艺。结果及结论试验结果表明所制备的布洛芬口腔崩解片崩解时间为35s,口感良好,溶出速度明显优于布洛芬普通片。     

黄芪口腔速崩片处方筛选

目的:筛选黄芪有效部位口腔速崩片的处方。方法:以药物溶出百分之五十的时间(t50)为考察指标,采用L9(34)正交表,选取主要辅料:MCC:L-HPC(A)、L-HPC(B)、甘露醇(C)、微粉硅胶(D)作为四因素,每一因素选择三水平。结果:黄芪口腔速崩片中辅料用量为:MCC:L-HPC为5∶1,L-HPC为3%,甘露醇为30%,微粉硅胶为0.1%。结论:此处方合理可行,可为黄芪有效部位口腔速崩片的进一步研究提供参考。     

盐酸小檗碱微囊口腔崩解片的制备与质量评价

目的制备盐酸小檗碱微囊口腔崩解片,并进行质量评价。方法以Eudragit E100作为囊材,MCC+PVPP为混合崩解剂,制备盐酸小檗碱微囊口腔崩解片,并测定崩解片中盐酸小檗碱的含量、崩解时间、溶出度和体外生物利用度。结果崩解片在口腔内平均崩解时间为(22±5)s,在p H=1.0、2.0的酸性介质中10 min内溶出超过70%,体外生物利用度与糖衣片差异无统计学意义。结论采用溶剂挥发法制备微囊,直接压片法制备口腔崩解片,工艺稳定可靠,质量评价符合药典要求。     

枸橼酸莫沙必利口腔崩解片的制备及评价

目的制备枸橼酸莫沙必利口腔崩解片并对其进行评价。方法在预实验的基础上选择处方中所用辅料,以口腔中崩解时间为考察指标,综合运用效应面图和等高线图对口腔崩解片处方进行优化,直接压片法压片,并对枸橼酸莫沙必利口腔崩解片溶出度进行了考察。结果枸橼酸莫沙必利口腔崩解片的最佳处方为枸橼酸莫沙必利5 mg、微晶纤维素76 mg、甘露醇97 mg、低取代羟丙基纤维素20 mg、橘子香精1 mg、硬脂酸富马酸钠1 mg。口腔中崩解时间为19.4 s,溶出度为99.7%。结论采用直接压片法制备枸橼酸莫沙必利口腔崩解片,崩解时间短、溶出速度快、口感好。     

多潘立酮口腔崩解片的处方优化及体外评价

目的:优化多潘立酮口腔崩解片的处方并评价其质量。方法:以直接粉末压片法制备多潘立酮口腔崩解片,采用HPLC法测定其含量,以崩解时限和体外溶出度为指标优化处方。结果:以6%的交联聚维酮作为崩解剂,制备的多潘立酮口腔崩解片外观圆整光洁,硬度为(3.3±0.8)kg/cm2,脆碎度<1%,体外崩解时限和口腔内崩解时限分别为(9.00±0.56),(17.00±2.00)s,15min的累积溶出度为(99.22±0.38)%。结论:按最优处方制备的多潘立酮口腔崩解片符合《中华人民共和国药典》2010年版的要求,质控方法准确可靠。     

对乙酰氨基酚口腔崩解片的研制

目的 以对乙酰氨基酚（扑热息痛）为模型药物制备新型口服速释剂型口腔崩解片。方法 以崩解时间为指标,采用正交试验筛选片剂的处方组成,并优化制备工艺。结果 以MCC／L-HPC 50：15作为崩解剂,部分制粒压片工艺制得的扑热息痛口腔崩解片,体外平均崩解时间为35s,置于口腔40s内可崩解,无砂砾感,片剂体外溶出度1min可达95％。结论 扑热息痛口腔崩解片于口腔内可迅速崩解,制备工艺简单可行,有效地改善了药物粉末的流动性,适宜于大生产。     

阿司匹林口崩片的制备

目的用正交实验法优选阿司匹林口腔崩解片的最佳处方和制备工艺。方法以崩解时间为主要评价指标,选择最佳制备工艺及配方,通过单因素试验选取变量,进行正交试验设计,确定最优处方,通过粉末直接压片制备样品。结果以崩解时间为评价指标筛选出了最佳处方组合,制得3批阿司匹林口腔速崩片,片面光洁圆整、无斑点,崩解时间为21±3 s。结论制备的阿司匹林口腔崩解片崩解时间短、硬度适中、口感好,具备临床应用价值。     

盐酸安非他酮缓释片处方筛选及体外释放评价

目的 筛选盐酸安非他酮缓释片的处方及缓释层包衣增重。方法 分别以盐酸安非他酮缓释片片芯的物理参数及缓释片的释放曲线为考察指标,通过调整片芯处方中填充剂、润滑剂、助流剂及缓释层包衣增重,确定了盐酸安非他酮缓释片的处方。结果 当片芯处方中采用微晶纤维素KG802、山嵛酸甘油酯和胶体二氧化硅时可获得片面较好的片芯,当处方中缓释层增重为4.0%时制得的缓释片分别在0.1 N盐酸溶液、pH 4.5醋酸盐和pH 6.8磷酸盐溶出介质中的释放曲线与原研制剂释放行为相似。结论 筛选的盐酸安非他酮缓释片处方合理。     

Preparation and evaluation of an orally fast disintegrating tablet formulation containing a hydrophobic drug

Abstract

Orally fast disintegrating tablets (FDTs or ODTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. Although the FDT area has passed its infancy, as shown by a large number of commercial products on the market, there are still many aspects to improve in the FDT formulations. Despite advances in the FDT technologies, formulation of hydrophobic drugs is still a challenge, especially when the amount of drug is high. In this study, a new solution is being developed to incorporate higher doses of a model hydrophobic drug; meloxicam, without affecting the fast disintegrating properties of the formulation. In order to enhance the solubilization of meloxicam in FDT formulations, β cyclodextrin inclusion complex of the drug is prepared and FDTs containing meloxicam--β cyclodextrin inclusion complex (F1 A and F2 A) were compared and evaluated with the FDTs containing pure meloxicam (F1 and F2) by means of in vitro quality control tests.     

Evaluation of disintegrating time of rapidly disintegrating tablets by a paddle method

A paddle method for measurement of the disintegrating time of orally disintegrating tablets with rizatriptan benzoate as a model drug was evaluated. The paddle method employed a dissolution test assembly with tablets immersed in disintegrating medium through a fastened sinker. Paddle stirring rate, opening of the sinker sieve, and tablet crushing strength influenced disintegrating time greatly. A logarithmic relationship was observed between disintegrating time and paddle revolution speed, while disintegrating time values and tablet crushing strength were fitted to a linear equation. The paddle method values with limited deviation were in good correlation with in vivo results. The paddle method was employed to optimize the disintegrating time of rizatriptan benzoate orally disintegrating tablets using a factorial design. The best-fit quadratic equation with a regression coefficient of 0.996 was highly predictive, which was indicative that the paddle method was precise and applicable in formulation optimization.     

咖啡因口崩片的研究

目的:本实验以咖啡因为模型药物,优化及研制咖啡因口腔崩解片.方法:采用低取代羟丙基纤维素、微晶纤维素(MCC)作为崩解剂,用干粉直接压片法制备咖啡因口腔崩解片.采用正交实验优化处方组成,以达到最短的崩解时间.通过质量研究,建立了初步的质量标准.结果:处方中主药咖啡因的含量固定为100 mg,MCC为40 mg,L-HPC为25 mg,甘露醇为105 mg,硬度固定在3 kg/cm2.按拟定的质量标准对咖啡因口崩片质量检查结果表明,咖啡因口崩片质量可控.结论:咖啡因口崩片的制剂简单、质量可控.     

苯甲酸利扎曲普坦口腔速崩片的制备

目的 制备苯甲酸利扎曲普坦口腔速崩片.方法 选用微晶纤维素(MCC)和低取代羟丙基纤维素(LHPC)作为崩解剂,通过粉末直接压片工艺制备口腔速崩片.考察速崩片的性质.结果 当MCC/LHPC的比例为9:1时,其体外崩解时间在20 s以内,体内崩解时间在30 s以内.结论 所制片剂口感良好,优化的工艺可以工业化生产.     

氟哌啶醇口腔崩解片的制备及质量评价

目的制备氟哌啶醇口腔崩解片,并评价其质量。方法直接粉末压片法制备口腔崩解片。以片剂崩解时限、口感为指标,采用正交实验设计优化处方,并对其溶出度进行检测。结果所得片剂完整光洁,口感良好,与市售普通片比较,口腔崩解片具有明显速释效果。结论氟哌啶醇口腔崩解片处方设计合理,制备工艺可行,产品质量可控。     

盐酸昂丹司琼口腔崩解片的制备以及崩解时间影响因素的考察

目的考察影响盐酸昂丹司琼口腔崩解片崩解时间的因素。方法采用湿法制粒压片法制备盐酸昂丹司琼的口腔崩解片,浆法测定崩解时间,考察了口腔崩解片的硬度、交联聚维酮（PVPP）和微晶纤维素（MCC）的用量对崩解时间的影响。结果片剂硬度与崩解时间成正比,交联聚维酮和微晶纤维素的用量与崩解时间成反比。调节片剂硬度为4．6kg／mm、交联聚维酮的用量为15～20mg／片和微晶纤维素的用量为50-70mg／片,可获得较理想的崩解时间和良好的片剂性质。结论湿法制粒压片法简便易行;制备的盐酸昂丹司琼口腔崩解片符合质量要求。     

盐酸氨溴索口腔崩解片制备工艺研究

目的设计制备盐酸氨溴索口腔崩解片。方法选用进口崩解剂,采用正交试验设计处方,用直接压片法制备盐酸氨溴索口腔崩解片。结果最佳处方为：微晶纤维素（进口）与甘露醇（1：3）;6%交联聚乙烯吡咯烷酮（进口）;0.8%枸橼酸为泡腾崩解剂;2%阿司帕坦;2%粉末香精。结论制备的盐酸氨溴索口腔崩解片矫味效果良好,崩解迅速,口感好。