托西酸舒他西林胶囊的制备工艺优化

目的优化托西酸舒他西林胶囊制备工艺,使其溶出度提高。方法将托西酸舒他西林原料微粉化,以超级羧甲淀粉钠为崩解剂,微粉硅胶为助流剂,湿法制粒制备托西酸舒他西林胶囊,以溶出度为指标进行综合评分,采用正交设计优化托西酸舒他西林的生产工艺。结果最佳处方为粉碎筛网目数200目、超级羧甲淀粉钠用量15%、二氧化硅用量4%。托西酸舒他西林胶囊溶出度平均达98.15%,加速试验考察6个月后溶出度仍在90%以上。结论托西酸舒他西林胶囊的制备工艺方便、科学,溶出度显著提高。     

依托贝特胶囊的制备及稳定性研究

目的：制备依托贝特胶囊,并对其稳定性进行考察。方法：从制剂的外观、胶囊内容物流动性、溶出度方面考察,对处方进行筛选优化,确定制备胶囊的原料药与辅料的最佳比例,并通过影响因素试验、加速稳定性试验和长期稳定性试验考察依托贝特胶囊的稳定性。结果：在最佳处方配比条件下,胶囊的外观、流动性、溶出度较理想。稳定性试验表明,上述条件下制备的胶囊各项考察指标与试验前比较,无明显的改变,稳定性较好。结论：依托贝特胶囊制备方法简单可靠,制备的胶囊稳定性好。     

琥乙红霉素胶囊处方工艺研究及溶出度测定

目的　琥乙红霉素胶囊处方筛选及溶出度测定。方法　通过正交试验筛选出胶囊剂的处方 ,采用硫酸比色法测定其溶出度。结果　最佳处方为 5 0 g·L-1的 CMC- Na、5 g交联 PVP、0 .5 g十二烷基硫酸钠、0 .5 g蔗糖酯 ;胶囊 30 min时溶出度大于 80 %。结论　组方合理 ,制备工艺简便易行 ,溶出度可控     

左氧氟沙星聚乙烯醇微粒胶囊的制备及稳定性研究

目的制备左氧氟沙星聚乙烯醇微粒胶囊并考察其稳定性。方法以聚乙烯醇为载体,采用喷雾干燥法制备左氧氟沙星聚乙烯醇微粒和分装胶囊,采用HPLC法测定左氧氟沙星含量,通过高温、高湿、强光,加速试验及长期试验分别进行稳定性考察。结果聚乙烯醇对左氧氟沙星HPLC法测定无干扰,HPLC测定误差≤0.9%,每粒胶囊平均含量为(100.55±1.11)%,胶囊70min体外溶出度约为(95.11±1.76)%,微粒中左氧氟沙星遇强光易分解,分装胶囊塑料瓶密封包装后,加速试验和长期试验检测指标变化不大,主药含量与体外溶出度基本保持不变。结论制剂制备及含量测定方法简便准确,稳定性良好,符合左氧氟沙星用药要求。     

辛伐他汀片处方筛选及稳定性研究

目的筛选辛伐他汀片处方、工艺,并考察其成品稳定性。方法以预胶化淀粉与微晶纤维素的比例、枸椽酸用量、粘合剂的浓度、羟丙纤维素用量为考察因素进行正交试验,以溶出度、含量等为成品质量考察指标进行综合评价;进行加速试验及长期试验考察成品的稳定性。结果最佳处方组成为预胶化淀粉与微晶纤维素为1∶1,枸椽酸0.3%,粘合剂的浓度为10%,低取代羟丙纤维素3%,采用干法制粒工艺制备;所得成品质量稳定。结论优选的辛伐他汀片处方、工艺合理,由其制备的成品溶出度、含量等均能达到标准要求。     

淀粉-阿司匹林颗粒生产工艺的改进

目的改进淀粉-阿司匹林颗粒的处方工艺,提高片剂的溶出度。方法在处方中增加聚维酮K30,用等量递加混合法增加物料的均一性。结果及结论改进后的淀粉-阿司匹林颗粒压片后溶出度≥90%,溶出度稳定性良好。     

巴洛沙星胶囊的制备工艺及溶出度研究

目的研制巴洛沙星胶囊并利用溶出度试验来严格控制产品的质量。方法采用单因素试验筛选巴洛沙星胶囊的处方、工艺,采用不同pH的溶出度试验条件检验处方的合理性。结果所研制的产品符合要求,在不同pH下,60min的溶出度达75％以上。结论制备工艺简单易行,药品溶出度较高。     

正交试验优选洛伐他汀胶囊处方工艺

目的:优选洛伐他汀胶囊处方工艺。方法:设计正交试验优选最佳制备条件并进行体外溶出度试验。结果:根据单因素分析及正交试验结果,得最佳处方:以10%聚乙烯吡咯烷酮为黏合剂、羧甲基淀粉钠内外加法(2∶1)为崩解剂,并以颗粒装囊,二次制粒时以75%乙醇为润湿剂。优选工艺所制胶囊30min体外溶出度在92%以上。结论:该制剂工艺稳定,重现性好,体外溶出速率高。     

阿维A胶囊处方筛选及稳定性研究

目的:筛选阿维A胶囊的最佳处方、工艺,并考察其成品的稳定性。方法:以可压性淀粉、乳糖、低取代羟丙基纤维素(L-HPC)处方用量为考察因素进行正交试验,以溶出度、流动性、含量均匀度等为成品质量考察指标进行综合评价;在光照、高温、高湿条件下对成品进行稳定性考察。结果:最佳处方组成为可压性淀粉20%、乳糖20%、L-HPC1%,采用制粒工艺制备;所得成品质量稳定。结论:优选的阿维A胶囊处方、工艺合理,由其制备的成品溶出度、含量均匀度、稳定性等均达《中国药典》要求。     

阿莫西林克拉维酸钾(7∶1)片处方、工艺研究及溶出度考察

目的:研究阿莫西林克拉维酸钾片处方及工艺,并考察其溶出度.方法:通过吸湿性试验、处方及工艺优化确定制备工艺,制备了阿莫西林克拉维酸钾片,用高效液相色谱法测定其溶出度并与进口薄膜衣片进行比较.结果:本制剂必须采用干法制粒压片工艺,制备环境湿度控制在33%以下,自制片与进口片溶出相当.结论:阿莫西林克拉维酸钾片处方工艺合理.     

Process optimization for the enhanced stability of diclofenac potassium granules and capsules

This study aimed to investigate the effects of different process parameters on the physical properties, in vitro dissolution rate, and short and long-term stability of diclofenac potassium (DFP) granules and capsules. DFP granules exhibited low total amounts of impurities when prepared through the wet granulation method using a granulating solvent with a low water/ethanol ratio. The impurities of the wet DFP mass dried at 70 °C were higher than those dried at 50 °C or 60 °C. DFP granules were stable under strong light exposure during preparation. DFP granules prepared using a granulating solvent with a 1:4 water/ethanol ratio had a relatively smaller particle size and higher angle of repose than those prepared using granulating solvents with other water/ethanol ratios. The dissolution rate of DFP capsules prepared using four different water/ethanol ratios was less than 2% after 10 min of dissolution and increased to 95% within 30 min of dissolution. The total amount of drug impurities of DFP capsules prepared using a granulating solvent with 1:4 water/ethanol ratio was considerably lower than those of DFP capsules prepared using a granulating solvent with a 1:0 water/ethanol solvent ratio. Regardless of the water/ethanol ratio, the capsules showed poor stability when exposed to high temperature (60 °C) and strong light (4500±500 Lux) for 10 days, but were relatively stable at high humidity (92.5% RH). The results of the long-term stability (25±2 °C and 60%±10% relative humidity) study showed that DFP granules were more stable than DFP capsules, and were stable for 12 months. The type of encapsulating material did not affect the 2-month stability of DFP. DFP granules are sensitive to granulating solvent and drying temperature and DFP capsules should be stored away from high temperature and strong light.     

阿克他利-羟丙基-β-环糊精包合物胶囊的制备及溶出度考察

目的:制备阿克他利-羟丙基-β-环糊精包合物胶囊,并考察其体外溶出性。方法:用搅拌法制备包合物,再分别以淀粉、微晶纤维素、乳糖、硫酸钙为填充剂制备包合物胶囊;采用转篮法对胶囊的溶出性进行考察,并与原料药及物理混合物比较。结果:与原料药及物理混合物比较,包合物的Td值更低(P<0.01);不同填充剂处方所制胶囊在15min内溶出均在75%以上。结论:阿克他利制成包合物后释放速度提高;4种填充剂所制包合物胶囊均能达到良好的溶出效果。     

Effects of various formulation factors on dissolution stability of aztreonam, hydrochlorothiazide, and sorivudine capsules

A split-split-plot 3² × 2² factorial design was used to study the effects of capsule filling machine and formulation factors such as lactose type, lubricant concentration, and capsule shell size on the dissolution stability of 50 mg potency hydrochlorothiazide (HCTZ), sorivudine (BV-araU), and aztreonam capsules packaged in HDPE bottles and stored under different conditions. It was observed that neither magnesium stearate concentration nor the type of capsule machine used to fill the capsule shells had any effect on dissolution stability of capsules of all three drugs for up to 6 months of storage at 50°C. For aztreonam, neither capsule shell size nor the type of lactose had any effect on dissolution stability. On the other hand, HCTZ size no. 1 capsules demonstrated better dissolution stability than size no. 2 capsules. Moreover, dissolution stability of capsules of sorivudine and HCTZ on storage at 50°C, 40°C/75% RH, and 40°C was dependent on the type of lactose used. HCTZ capsules containing Fast-Flo^® lactose, hydrous lactose, or anhydrous lactose showed up to 45, 25, and 10% decrease in dissolution, respectively, compared to initial values, at the 20 min dissolution time point after 6 months storage at 50°C. The extent of decrease in the dissolution rate was less under the conditions of storage at 40°C/75% RH and 40°C. Similar effects of decrease in the dissolution rate with the different types of lactose were observed with sorivudine, although to a much lesser degree compared to HCTZ capsules. No decrease in dissolution rate was observed for any drug after 20 months storage at 30°C. It was hypothesized that the slight decrease in dissolution rate of sorivudine capsules was due to significant caking of the capsule contents in the presence of the moisture liberated from the excipients and the capsule shells. For aztreonam capsules, the caking of their contents was without any discernable effect on dissolution because of the high aqueous solubility. In contrast, for HCTZ capsules, changes in dissolution rate were far too pronounced to be attributed to caking only.     

Comparative in vivo bioequivalence and in vitro dissolution of two cyclosporin A soft gelatin capsule formulations

OBJECTIVE: A study was conducted to establish the bioequivalence between a newly developed cyclosporin A (CsA) oral formulation, Deximune soft-gelatin capsules (Dexcel Ltd.) and Sandimmune Neoral (Novartis Inc.). MATERIALS AND METHODS: The clinical investigation was designed as a randomized, open-labeled, two-period, two-treatment crossover study, in 24 healthy fasted male volunteers. The subjects were administered a single 200 mg CsA dose of either formulation. Serial venous blood samples were obtained over 24 hours after each administration to measure CsA in whole blood by a specific TDx-immunoassay. In addition, the comparative drug release rate was assessed using a dissolution apparatus test according to the USP-24 method. RESULTS: For both treatments, a mean maximum blood concentration (Cmax) of approximately 1,200 ng/ml was obtained at about 1.6 hours (tmax) after administration and the geometric mean of the area under the blood concentration-time curve (AUC) both for test and reference was approximately 4,900 ng x h/ml. Bioequivalence was conclusively demonstrated for both rate (Cmax and tmax) and extent (AUC) of CsA absorption, between the two treatments. Moreover, the CsA blood concentration measurement at 2 hours after administration (C2), demonstrated equivalent results between the two products. The point estimates and their 90% confidence intervals were within the respective equivalence ranges for the pharmacokinetic parameters and were included in the range for drugs with a narrow therapeutic index. The comparative dissolution test for both formulations showed an in vitro release rate of more than 90% within 15 minutes. CONCLUSIONS: Based on the results, the two oral CsA formulations compared are bioequivalent and can be interchanged without need for dosage adjustment.     

Alginate-based pellets prepared by extrusion/spheronization: a preliminary study on the effect of additive in granulating liquid.

The aim of this study was to investigate the possibility of producing alginate-based pellets by extrusion/spheronization and also to improve the formation of spherical alginate-based pellets by investigating the effect of additive in granulating liquid on characteristics and drug release from resulting pellets. Two types of sodium alginate (30%) were evaluated in combination with theophylline (20%), microcrystalline cellulose (50%) and different granulation liquids. The pellets were then prepared in a basket extruder, then spheronized and dried. The final products were characterized by morphological examination and drug release study. Different additives in the granulating liquid influenced the ability of the extruded mass to form pellets (the processability) with this technique. However, different sodium alginate types responded to shape modifications to a different extent. Long, dumbbell-shaped pellets were obtained with viscous granulating liquids. However, short, nearly spherical pellets were obtained with watery granulation liquid with calcium chloride that reduced the swelling ability of sodium alginate. Improvements in the pellet characteristics were also dependent on the sodium alginate type employed. Most of pellet formulations released about 75-85% drug within 60min and showed a good fit into both Higuchi and Korsmeyer-Peppas equations. Higher amount of 3% calcium chloride, as a granulating liquid, in the formulation showed higher mean dissolution time resulting from the cross-linking properties of calcium ions to the negative charges of alginate molecules.     

Differentiating factors between oral fast-dissolving technologies

The oral fast-dissolving systems are defined as oral drug delivery systems that dissolve or disintegrate within a few seconds to a few minutes of placement in the mouth and that do not require water to aid swallowing. Various technologies are used to achieve quick dissolution/dispersion in the oral cavity. This review focuses on the properties of the various fast-dissolving (orally disintegrating) technologies for systemic drug delivery. Freeze-drying, molding, and compaction technologies are described. Zydis®, Quicksolv® and Lyoc® are prepared by freeze drying; FlashDose® is prepared by a molding/cotton-candy process; WOWTAB®, FlashTab® and Frosta® are prepared by granulation followed by compression; OraSolv®, DuraSolv®, OraVescent®, QDis?, Ziplets® and AdvaTab? are prepared by direct compression. Differences between drug delivery systems with regard to their composition (excipients), structure and formulation are also reviewed. Employment of relatively consolidated technologies (lyophilization, compaction, and granulation) can shorten the formulation, development, and scaling-up processes. In addition, the properties of systems prepared using these technologies are critically compared. The advantages and the disadvantages of each type of dosage form in terms of dissolution and absorption rate, bioavailability, stability, mechanical strength, taste-masking properties, and patient compliance are emphasized. The implications of these differences for patient compliance and choice of technologies in drug formulation are highlighted. Freeze-drying allows immediate dissolution of the tablets because of their high porosity, and enhances drug stability, especially for moisture-sensitive substances; on the other hand, a porous network is associated with low physical resistance and high friability, and special packaging is required in some cases. Use of the molding technology results in tablets with an appropriate dissolution time, even though they are characterized by poor mechanical properties (hardness). The fast-dissolving tablets based on compaction technologies utilize consolidated technologies (standard equipment and materials) and their production costs are low. Most of these tablets are characterized by good physical resistance (hardness), although this can result in an increase in the disintegration time. Apart from its favorable anatomic and physiologic features that allow modulation of drug permeation, the high degree of vascularization, minimal enzymatic pool and potential to avoid first-pass metabolism make the oral cavity an ideal site for peptide/protein delivery and absorption using fast-dissolving formulations. Furthermore, the gentle preparation procedures and technologies (in particular lyophilization) used in the manufacture of oral fast-dissolving tablets are compatible with the delicate drug substances delivered by these formulations.     

The influence of polymorphism on the manufacturability and in vitro dissolution of sulindac-containing hard gelatin capsules

Abstract

Context: Drug polymorphism could affect drug product dissolution, manufacturability, stability and bioavailability/bioequivalence. The impact of polymorphism on the manufacturability and in vitro dissolution profiles of sulindac capsules has not been studied yet.

Objective: To evaluate the impact of polymorphism on the manufacturability and in vitro dissolution of sulindac hard gelatin capsules.

Materials and methods: Sulindac crystal forms I and II (SLDI and SLDII, respectively) were prepared and characterized. Powder formulations containing one of the polymorphs, lactose and magnesium stearate (at three different levels) were prepared and their flow properties determined. Hard gelatin capsules were filled with the formulations and tested for fill-weight variations. Drug dissolution for SLDI- and SLDII-containing hard gelatin capsules was determined.

Results: Differences in flow properties for each polymorph were observed, as well as for their formulations, which in turn affected capsule weight homogeneity. Statistically significant differences in the rate and extent of drug release were observed between SLDI- and SLDII-containing capsules.

Discussion: Formulations containing SLDI showed a better manufacturability and a better dissolution profile than those with SLDII.

Conclusion: Sulindac crystalline form I was the best candidate for hard gelatin capsule formulation because of its technological and in vitro dissolution properties.