浒苔微晶纤维素的制备及其在药用辅料中的应用

目的 浒苔是一种常见的多细胞绿藻,属于石莼科,是绿潮的主要组成物质,为了更好的利用浒苔资源,缓解绿潮带来的生态问题,本文利用浒苔为原料制备微晶纤维素,并探究其作为辅料进行压片的优势。方法 以浒苔为原料制备微晶纤维素并检测其外观,官能团与电导率等理化性质,再以微晶纤维素作辅料以阿司匹林作为主药进行压片,并对其质量进行检查。结果 微晶纤维素的理化指标均符合《中国药典》2020年版规定,且与市售微晶纤维素具有相同或相似官能团结构;以微晶纤维素作辅料制备的片剂色泽均匀,具有适宜的硬度与耐磨性。     

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。     

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。     

盐酸托烷司琼口腔崩解片的制备

目的 制备并评价盐酸托烷司琼口腔崩解片.方法 选择辅料,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,直接压片法压片后,考察盐酸托烷司琼口腔崩解片的溶出度.结果 所用处方为5 mg盐酸托烷司琼、78 mg微晶纤维素、95 mg甘露醇、20 mg交联羧甲基纤维素钠、1.6 mg草莓香精、0.4 mg硬脂酸镁.口腔中崩解时间为22.8 s,溶出度为97.4%.结论 采用直接压片法制备的盐酸托烷司琼口腔崩解片崩解时间短、溶出速度快.     

恩替卡韦口腔崩解片的制备及质量研究

目的:制备恩替卡韦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,并对恩替卡韦口腔崩解片溶出度进行了考察。结果:优化后的处方为恩替卡韦0.5 mg、微晶纤维素77 mg,甘露醇97 mg、交联羧甲基纤维素钠20 mg、苹果香精5 mg、硬脂酸镁0.5 mg,口腔中崩解时间为27.4 s,溶出度为98.6%。结论:采用直接压片法制备恩替卡韦口腔崩解片,崩解时间短、溶出速度快。     

吲哚美辛肠溶分散片的制备及性质探讨

制备了吲哚美辛肠溶分散片 ,考察辅料对其崩解时限及溶出速度的影响。结果显示 ,当处方中低取代羟丙纤维素与微晶纤维素的比例为 3∶ 2、海藻酸钠用量为 1%时 ,吲哚美辛肠溶分散片的崩解时间最短 (33± 3s) ,在人工肠液中的溶出速度明显快于市售肠溶片剂和市售胶囊。     

基于预混辅料的拉莫三嗪口腔崩解片的制备

目的由预混辅料入手,制备拉莫三嗪口腔崩解片。方法以异麦芽酮糖醇、微晶纤维素和交联聚维酮为主要辅料,使用湿法制粒的方法制备预混辅料,并测定了预混辅料产品的粉体学性质。选用拉莫三嗪为主药,与预混辅料及少量崩解剂、润滑剂和矫味剂,通过粉末直压的方法制备拉莫三嗪口腔崩解片,并对拉莫三嗪口腔崩解片进行基本的体外评价。结果通过单因素考察和正交试验,预混辅料的最终处方组成为:异麦芽酮糖醇与微晶纤维素的比例为3∶4,加入8%交联聚维酮。拉莫三嗪口腔崩解片的最优处方组成(按1 000片计)为:25 g拉莫三嗪,137 g预混辅料,14.4 g低取代羟丙基纤维素,1.8 g硬脂酸镁,1.8 g矫味剂。拉莫三嗪口腔崩解片的崩解时限为35 s,且在5 min内溶出完全。结论根据试验,制备的预混辅料的性质优良,口腔崩解片的崩解时限、口感和溶出度等均符合规定。     

曲克芦丁口腔崩解片的研制及质量评价

目的制备曲克芦丁口腔崩解片并进行质量评价。方法以微晶纤维素、乳糖和甘露醇为主要辅料,通过正交试验优化处方,采用直接压片法制备口腔崩解片,并对其崩解时限、口感进行考察。结果制备1000片曲克芦丁口腔崩解片的最佳处方为曲克芦丁100g、微晶纤维素50g、乳糖10g、甘露醇15g、交联羧甲纤维素钠5g、甜菊素3g、枸橼酸0.5g、碳酸氢钠0.5g、硬脂酸镁1.0g。制得的口腔崩解片在30s内能完全崩解。结论制备的曲克芦丁口腔崩解片为快速崩解型片剂,制备工艺方法可行,符合用药要求。     

氯氮平HP-β-环糊精包合物及其口腔崩解片的制备与评价

目的制备氯氮平环糊精包合物口腔崩解片,确定其处方并进行质量评价。方法将氯氮平制成HP-β-CD包合物,正交设计法选择崩解剂、填充剂后制成口腔崩解片,考察崩解片的崩解时间、溶出度等指标,优选片剂辅料。结果氯氮平包合物包封率和载药量分别为71.12%、18.52%,以甘露醇、微晶纤维素、羧甲基淀粉钠为辅料制备的氯氮平口腔崩解片崩解时间<1 min,累积溶出度101.5%。结论选定辅料可用于制备氯氮平HP-β-CD包合物口腔崩解片,质量符合要求。     

盐酸氨溴索口腔崩解片的制备及质量评价

目的:制备盐酸氨溴索口腔崩解片并对其进行质量评价。方法:以甘露醇为主要辅料制备口腔崩解片,采用分光光度法测定氨溴索含量,并对崩解时限、口感、溶出度进行考查、测定。结果:最佳处方为微晶纤维素50g、甘露醇20g、羟丙基纤维素10g、碳酸氢钠2g;氨溴索检测浓度线性范围为0.005~0.030mg/ml(r=0.9999),平均回收率为100.50%,平均RSD=0.71;成品在30s内崩解完全。结论:该制剂具有快速崩解作用,并与市售片等效。     

Compression of Controlled-Release Pellets Produced by a Hot-Melt Extrusion and Spheronization Process

The purpose of this study was to investigate the physicomechanical and dissolution properties of tablets containing controlled-release pellets prepared by a hot-melt extrusion and spheronization process. A powder blend of anhydrous theophylline, Eudragit® Preparation 4135 F, and functional excipients was melt-extruded, pelletized, and then spheronized. The pellets were compressed into tablets using forces of 5, 10, 15, and 20 kN. Tablet diluents included microcrystalline cellulose, a mixture of spray-dried lactose and microcrystalline cellulose, modified food starch, and soy polysaccharides. The effective porosity of the compressed pellets was measured using mercury porosimetry and helium pycnometry, while the surface area was determined using Brunauer, Emmett, and Teller (BET) analysis. The disintegration time, hardness, and friability of compacts were determined. Drug release studies were performed according to USP 27 Apparatus 3 guidelines in 250 mL of medium (pH 1.0, 3.0, 5.0, 6.8, and 7.4) 37°C and 20 dpm. Samples were analyzed by high pressure-liquid chromatography (HPLC). Effective porosity and surface area determinations of the melt-extruded pellets were not influenced by compression. The percent of theophylline released from rapidly disintegrating tablets was not affected by compression force or excipient selection, but tablets with prolonged disintegration times exhibited delayed drug release in acidic media. However, dissolution profiles of uncompressed pellets and all compacts were identical after transition from 0.1 N HCl to media increasing in pH from 3.0 to 7.4. Furthermore, pellet to filler excipient ratio and filler excipient selection did not influence the rate of drug release from compacts.     

Compression of controlled-release pellets produced by a hot-melt extrusion and spheronization process

The purpose of this study was to investigate the physicomechanical and dissolution properties of tablets containing controlled-release pellets prepared by a hot-melt extrusion and spheronization process. A powder blend of anhydrous theophylline, Eudragit Preparation 4135 F, and functional excipients was melt-extruded, pelletized, and then spheronized. The pellets were compressed into tablets using forces of 5, 10, 15, and 20 kN. Tablet diluents included microcrystalline cellulose, a mixture of spray-dried lactose and microcrystalline cellulose, modified food starch, and soy polysaccharides. The effective porosity of the compressed pellets was measured using mercury porosimetry and helium pycnometry, while the surface area was determined using Brunauer, Emmett, and Teller (BET) analysis. The disintegration time, hardness, and friability of compacts were determined. Drug release studies were performed according to USP 27 Apparatus 3 guidelines in 250 mL of medium (pH 1.0, 3.0, 5.0, 6.8, and 7.4) 37 degrees C and 20 dpm. Samples were analyzed by high pressure-liquid chromatography (HPLC). Effective porosity and surface area determinations of the melt-extruded pellets were not influenced by compression. The percent of theophylline released from rapidly disintegrating tablets was not affected by compression force or excipient selection, but tablets with prolonged disintegration times exhibited delayed drug release in acidic media. However, dissolution profiles of uncompressed pellets and all compacts were identical after transition from 0.1 N HCl to media increasing in pH from 3.0 to 7.4. Furthermore, pellet to filler excipient ratio and filler excipient selection did not influence the rate of drug release from compacts.     

Development of Orodispersible Tizanidine HCl Tablets Using Spray Dried Coprocessed Exipient Bases

Tizanidine HCl is a centrally acting α-2 adrenergic agonist muscle relaxant with a slightly bitter taste having short half-life of 2.5 h. In the present study effect of co-processed excipient bases in formulation of orodispersible tizanidine HCl tablets by direct compression method was investigated. Co-processed excipient of microcrystalline cellulose with SSL-hydroxypropylcellulose was prepared using spray drier in 1:1, 1:2 and 1:3 ratio. Formulated tablets were evaluated for hardness, friability, in vitro disintegration time and in vitro drug release. Formulation F-3 prepared by addition of co-processed excipient base in ratio of 1:3 showed minimum disintegration time of 9.15±0.04 s and higher amount of drug release of 93.75% at the end of 15 min. Granules obtained by spray drying technique were found to be more spherical which improved its flow property and was supported by scanning electron microscope studies. Thermal studies indicated change in amorphous state, compatibility of drug in formulation was confirmed by fourier transform infrared studies. Analyses of drug release data indicated formulation followed first order kinetics. Inclusion of co-processed excipient base in formulation of orodispersible tablets enhanced disintegration significantly.     

Preliminary studies of the development of a direct compression cellulose excipient from bagasse

Bagasse is an unused by-product in cane sugar manufacture. Bagasse from sugar cane manually harvested in Indonesia was transformed to pulp by mechanical means and repeated autoclaving in 1.4% NaOH. It was then subjected to cycles of bleaching with hypochlorite and acid hydrolysis with 2.5 M HCl to produce 'microcrystalline' cellulose (MCC). Extraction of waxes by petroleum ether was necessary in order to improve the disintegration properties of tablets made from this material, DICEB III. When the bagasse-derived cellulose was reconstituted by recombining different proportions of selected sieve cuts to have a similar sieve size distribution as the commercially available MCC, Avicel PH102, it was found that the latter and DICEB III also had similar crystallinity as measured by X-ray powder diffraction (degree of crystallinity 2.8 +/- 0.2). The crystallinity and flow index were also relatively insensitive to most of the changes in the manufacturing procedure, indicating that the production process was quite robust. Directly compressed tablets were made containing 50 mg of caffeine and 500 mg of either Avicel PH102 or DICEB III to approximately the same hardness (11.6 +/- 1.1 and 13.7 +/- 0.5 kPa, respectively). They displayed similar satisfactory disintegration and dissolution behavior. However, DICEB III required greater compaction pressures than Avicel PH102, perhaps because the former was not spray dried to give spherical agglomerates of particles of uniform size as the commercial product. Rather, DICEB III consisted mainly of single irregular particles. Further work is required to improve the new excipient and to explore if the bagasse from mechanically harvested sugar cane (often contaminated by soil) could also be used for production of MCC.     

An evaluation of microcrystalline cellulose and lactose excipients using an instrumented single station tablet press

The objective of this study was to evaluate the effects of microcrystalline cellulose of two particle sizes from two suppliers at two concentration levels, in combination with anhydrous lactose or Fast-Flo lactose on various properties of hydrochlorothiazide tablets. The powder blends before compression were evaluated for flow, density and compressibility. Tablets were compressed at three hardnesses and evaluated for friability, disintegration and hydrochlorothiazide dissolution. Powder blends containing Fast-Flo lactose exhibited a flow rate predicted to be sufficient for high-speed tableting whereas only when anhydrous lactose was used with the larger particle size microcrystalline cellulose was the same degree of flowability obtained. Density was affected by the concentration of microcrystalline cellulose. Fast-Flo lactose markedly increased density at the lower level of microcrystalline cellulose concentration. No difference was found in blend compressibility as a result of microcrystalline cellulose particle size or supplier source at medium to high tablet hardness levels, however, anhydrous lactose blends were more compressible than Fast-Flo lactose blends. At all hardness levels, tablets from all blends exhibited excellent friability. In most instances, tablet disintegration seemed to be more rapid when Fast-Flo lactose was present. Hydrochlorothiazide dissolution from all tablets easily met USP specifications. The microcrystalline cellulose from the two sources are interchangeable within particle size classification. Anhydrous lactose is more compressible than Fast-Flo lactose but Fast-Flo lactose is more flowable and its use results in more rapid drug dissolution at the higher microcrystalline cellulose levels.     

Comparison of statistical analysis and Bayesian Networks in the evaluation of dissolution performance of BCS Class II model drugs

This project compared the effect of formulation variables on the dissolution performance of model Biopharmaceutics Classification System (BCS) Class II drugs from hard gelatin capsules using statistical analysis and Bayesian networks. The drugs chosen for this study were carbamazepine (CAR), chlorpropamide (CHL), diazepam (DIA), ketoprofen (KET), and naproxen (NAP). Formulations contained anhydrous lactose, microcrystalline cellulose, sodium stearyl fumerate, sodium lauryl sulfate, and croscarmellose sodium. A Box-Behnken experimental design was used in the statistical analysis. The weakly acidic drugs were tested using USP apparatus II with capsule sinkers in 0.1M pH 6.8 Potassium Phosphate buffer. The weakly basic drugs were tested using USP apparatus I in 0.1N HCl buffer. Mean dissolution profiles were compared via calculation of the similarity factor. The Box-Behnken experimental design was found to be useful in assessing primary and secondary excipient effects on dissolution. The Bayesian Network developed for the dataset mirrored the key excipient effects on dissolution performance.     

Simultaneous production and co-mixing of microparticles of nevirapine with excipients by supercritical antisolvent method for dissolution enhancement

Microparticles of a poorly water-soluble model drug, nevirapine (NEV) were prepared by supercritical antisolvent (SAS) method and simultaneously deposited on the surface of excipients such as lactose and microcrystalline cellulose in a single step to reduce drug–drug particle aggregation. In the proposed method, termed supercritical antisolvent-drug excipient mixing (SAS-DEM), drug particles were precipitated in supercritical CO₂ vessel containing excipient particles in suspended state. Drug/excipient mixtures were characterized for surface morphology, crystallinity, drug–excipient physico-chemical interactions, and molecular state of drug. In addition, the drug content uniformity and dissolution rate were determined. A highly ordered NEV–excipient mixture was produced. The SAS-DEM treatment was effective in overcoming drug–drug particle aggregation and did not affect the crystallinity or physico-chemical properties of NEV. The produced drug/excipient mixture has a significantly faster dissolution rate as compared to SAS drug microparticles alone or when physically mixed with the excipients.     

Co-processed MCC-Eudragit® E excipients for extrusion-spheronization

This study investigates the extrusion-spheronization performance of some mixtures of co-processed microcrystalline cellulose and Eudragit® E (as excipients) and sorbitol (as soluble filler-disintegrant). Attention is focused on the dissolution rate of low water solubility drugs (hydrochlorothiazide is used as a model drug) from pellets prepared with these mixtures. All pellet formulations studied presented adequate morphological, flow and mechanical properties. The pellets prepared with co-processed MCC-Eudragit® E and sorbitol show a drug dissolution rate dependent on the content of Eudragit® E in the co-processed excipient and on the proportion of sorbitol incorporated. Furthermore, the pellets made with co-processed MCC-Eudragit® E incorporating the higher proportion of sorbitol (50%) show a very high dissolution rate of hydrochlorothiazide (HCT) and undergo rapid disintegration in the dissolution medium.     

Influence of excipients,drugs, and osmotic agent in the inner core on the time-controlled disintegration of compression-coated ethylcellulose tablets

The effect of excipient, drug, and osmotic agent loaded in the inner core tablet on the time-controlled disintegration of compression-coated tablet prepared by direct compression with micronized ethylcellulose was investigated. The excipients [spray-dried lactose, hydroxypropyl methyl cellulose, sodium starch glycolate, microcrystalline cellulose, different drugs (sodium diclofenac: model drug, salbutamol sulfate, and theophylline anhydrate) and osmotic agent (sodium chloride)] were used to formulate the composition of the inner core tablet. The result indicates that drug release from all the compression-coated tablets was characterized by a distinctive lag of time followed by a faster drug release, dependent on the types of excipient and drug, and osmotic agent used in the inner core tablet. Respectively, the lag of time was 8.5, 12.4, 14.6, or 15.8 h for spray-dried lactose, hydroxypropyl methyl cellulose, sodium starch glycolate, or microcrystalline cellulose-loaded inner core tablet, as compared with 16.4 h for an inner core made of sodium diclofenac alone. The direct-compressible excipients such as spray-dried lactose, sodium starch glycolate, and microcrystalline cellulose seemed not to illustrate a marked disintegration function to rapidly rapture the outer coating layer. The lag of time was only slightly shortened from 16.4 to 14.6 h, >24 to 17.8 h, or >24 to 21.3 h for sodium diclofenac, theophylline anhydrate, or salbutamol sulfate incorporated with sodium starch glycolate into the inner core tablet, respectively, suggesting that sodium starch glycolate did not perform its superdisintegration. Once an osmotic agent of sodium chloride was incorporated into the inner core tablet, the lag of time for the compression-coated tablet was markedly shortened to <1 h, as compared with 16.4 h for drug alone. The more the amount of sodium chloride added, the less the time of lag obtained. Osmotic pressure did have a key role in controlling the drug dissolution. The present result implies that osmotic function is more suitable than superdisintegration function in designing a compression-coated tablet with time-controlled disintegration.