丹皮酚-SPE_7-β-CD包合物片剂的处方研究

目的:优化丹皮酚-SPE7-β-环糊精(CD)包合物片剂的处方。方法:以溶出度为指标,黏合剂10%淀粉浆、崩解剂干淀粉和润滑剂硬脂酸镁的用量为主要考察因素,采用正交试验筛选最佳处方,并进行验证试验。结果:最佳处方为丹皮酚-SPE7-β-CD106.2g、乳糖48.7g、10%淀粉浆3.0g、干淀粉6.0g、硬脂酸镁0.1g,所制3批样品溶出度均值为95.56%。结论:该优化处方较为理想,可行性较强。     

Punch geometry and formulation considerations in reducing tablet friability and their effect on in vitro dissolution.

The tablet friability resulting from formulation variations was studied under controlled granulation moisture content and tablet crushing strength. Tablets made with lactose were more friable than tablets made with microcrystalline cellulose. Replacement of 0.5% magnesium stearate with 0.5% stearic acid in the formula reduced tablet friability, whereas the combination of 0.5% stearic acid and up to 0.25% magnesium stearate did not increase tablet friability, decrease drug dissolution rate, or increase tablet-to-tablet variability in dissolution. Tablets compressed with extra deep concave punches resulted in lower friability compared with tablets compressed with standard concave or deep concave punches. The friabilities of the standard convex and deep convex tablets were similar, indicating that a critical level of punch tip curvature was important in reducing tablet friability. The dissolution rate was not affected by the punch tip geometry, but the tablet-to-tablet dissolution variability at the 0.5% stearic acid level for the extra deep convex tablets was higher compared with the standard convex tablets.     

马来酸氨氯地平分散片处方及制备工艺研究分析

目的探讨马来酸氨氯地平分散片的处方以及制备工艺。方法通过实验对马来酸氨氯地平分散片的处方以及制备工艺进行研究。结果使用交联聚维酮和低取代羟并纤维素为崩解剂,预胶化淀粉和微晶纤维素作为填充剂,使用聚维酮-K30作为粘合剂以及二氧化硅和硬脂酸镁为润滑剂制成的马来酸氨氯地平分散片,可以在3min内崩解,并且能够通过2号筛,硬度适中,成型性好,外观光洁,可以迅速的分散,符合《中国药典》对分散片的要求。结论马来酸氨氯地平分散片符合分散片的制剂要求,溶出度比较高,崩解迅速,制备工艺简单,符合大规模生产要求。     

布洛芬口腔崩解片的制备及质量检查

采用正交设计筛选布洛芬口腔崩解片的处方并考察片剂质量.所得优化处方为(%):交联羧甲纤维素钠6、枸橼酸0.5、吐温-80 0.02、香精2,氯化钠2、阿斯巴甜3、微粉硅胶1、硬脂酸镁0.5.所得片剂30s内完全崩解,3min释药80%以上,口感良好.     

非那雄胺片制剂的处方及工艺研究

目的：对非那雄胺片（1mg）的处方工艺进行研究。方法：参照国外英文说明书中制剂所用的辅料,通过测定在四种不同溶出介质中的溶出曲线,使之达到与原研市售品溶出曲线相似,判断增溶剂、崩解剂、填充剂的用量及工艺进行考察,并对确定处方及制备工艺中试三批,测定在四种溶出介质中的溶出曲线、含量均匀度和有关物质等指标。结果：用非那雄胺为主药,以乳糖、微晶纤维素和预胶化淀粉为填充剂,以泊洛沙姆188为增溶剂,以羧甲淀粉钠为崩解剂,以硬脂酸镁为润滑剂,以胃溶型薄膜包衣预混剂为包衣材料,制得非那雄胺片。结论：本制剂工艺稳定,各种辅料均有合法来源,制得非那雄胺片（1mg）与原研市售品溶出行为相似。     

甲磺酸伊马替尼片处方工艺研究

目的：研究甲磺酸伊马替尼片的处方工艺。方法：以制剂的溶出曲线为指标,筛选甲磺酸伊马替尼片处方和制备工艺。结果：建立了以微晶纤维素、交联聚维酮和硬脂酸镁为辅料的处方及采用95%乙醇湿法制粒的工艺,制备的3批产品的有关物质、溶出度等指标与参比制剂具有相似性,制剂特性满足制剂质量一致性的要求。结论：甲磺酸伊马替尼片处方合理,工艺简单,易于工业化生产。     

Search for technological reasons to develop a capsule or a tablet formulation with respect to wettability and dissolution

Proquazone, a poorly wettable compound, was used as a model drug in the search for reasons to develop a capsule or tablet formulation. The capsules were filled with proquazone as active ingredient, with lactose monohydrate (200 mesh) as filler and with magnesium stearate as lubricant. The tablet was made out of a granulate as internal phase which consisted of proquazone as active ingredient, lactose as filler, corn starch as disintegrant and PVP as a binding agent. The external phase consisted of magnesium stearate and corn starch. The concentration of proquazone in the capsule and in the tablet formulation was varied. The capsule formulations showed a significantly slower dissolution of the drug substance than the tablet formulations especially for a high-drug load. Independently of the drug load, only the tablet formulation showed a high-dissolution rate. Thus, concerning drug load, only the tablet formulations showed to be robust. It became clear that proquazone needs to be formulated as a granulate or a tablet to achieve a fast dissolution rate. Thus, a poorly wettable drug, especially when it is found in high concentrations, can have direct impact on the decision to develop a tablet or a capsule formulation.     

Evaluation of changes in drug particle size during tableting by measurement of dissolution of disintegrated tablets.

Three poorly soluble drugs (chloramphenicol, phenacetin and prednisolone) were compressed into tablets of 10% drug content on a physical testing instrument at three different compression pressures. The dissolution profiles were determined by a modification of the U.S.P. method for drug suspensions, granules before compression, disintegrated and intact tablets. By comparison of the dissolution rates for disintegrated tablets with those for granules before compression, or suspensions, it is possible to separate the change in particle size during compression from the pressure-dependent dissolution behaviour of intact tablets. A comparative measurement of dissolution for disintegrated tablets with that for granules provides a useful method for elucidating the particle bonding or cleavage within the tablet during compression.     

Evaluation of changes in drug particle size during tableting by measurement of dissolution of disintegrated tablets

Three poorly soluble drugs (chloramphenicol, phenacetin and prednisolone) were compressed into tablets of 10% drug content on a physical testing instrument at three different compression pressures. The dissolution profiles were determined by a modification of the U.S.P. method for drug suspensions, granules before compression, disintegrated and intact tablets. By comparison of the dissolution rates for disintegrated tablets with those for granules before compression, or suspensions, it is possible to separate the change in particle size during compression from the pressure-dependent dissolution behaviour of intact tablets. A comparative measurement of dissolution for disintegrated tablets with that for granules provides a useful method for elucidating the particle bonding or cleavage within the tablet during compression.     

Drug-excipient interactions resulting from powder mixing. III: Solid state properties and their effect on drug dissolution

Micronized prednisone was used to study the effect of powder mixing on drug-excipient interactions and their effect on in vitro dissolution from uncompacted, hand-filled capsules. Two powder formulations contained CaHPO4 X 2H2O (dibasic calcium phosphate dihydrate) as a filler and potato starch or sodium starch glycolate as a disintegrant. The third powder formulation contained pregelatinized starch as a disintegrant/filler. The lubricant in these formulations was magnesium stearate. When drug, CaHPO4 X 2H2O, and the disintegrant were thoroughly mixed and hand filled into capsules without compaction, only approximately 70% of the drug dissolved in 30 min. The incomplete dissolution of the drug was caused by the formation of agglomerates and the inclusion of the drug particles by these agglomerates. In contrast, when a mixture of drug and pregelatinized starch was used, complete dissolution of the drug was achieved after 30 min due to the absence of agglomeration and inclusion. Prolonged mixing of the formulation containing CaHPO4 X 2H2O with magnesium stearate resulted in a decrease in the dissolution rate. The total amount of the drug dissolved at the end of 30 min was reduced from 70 to 20%. The decrease in the rate of drug dissolution resulted from drug-excipient interactions which caused flaking of the magnesium stearate particles. The adhesion of these flakes to the drug particles and drug-excipient agglomerates resulted in hydrophobic coating which reduced water penetration. The rate of drug dissolution was not affected when drug and pregelatinized starch were mixed with magnesium stearate for a prolonged time due to the absence of magnesium stearate flaking and film formation.     

硬脂酸镁过度润滑作用对盐酸二甲双胍缓释片的影响

目的 考察硬脂酸镁过度润滑作用对盐酸二甲双胍缓释片的影响。方法 通过改变硬脂酸镁的用量、改变硬脂酸镁的混合时间、改变加料器转速,制备不同盐酸二甲双胍缓释片。通过对比总混颗粒的粉体性质、片剂的溶出。综合评价硬脂酸镁过度润滑对盐酸二甲双胍缓释片的影响。结果 增加硬脂酸镁的用量、延长总混时间、加快加料器的转速均会导致硬脂酸镁过度润滑。表现为颗粒流动性并未明显改善,但可压性显著下降,盐酸二甲双胍缓释片溶出无明显减缓。结论 盐酸二甲双胍缓释片的可压性对硬脂酸镁的润滑作用敏感,需控制硬脂酸镁的用量、混合的时间以及加料器的转述,防止过度润滑,造成可压性变差的现象产生。     

Investigation of excipient type and level on drug release from controlled release tablets containing HPMC

The purpose of this study was to investigate the influence of excipient type and level on the release of alprazolam formulated in controlled release matrix tablets containing hydroxypropyl methylcellulose (HPMC). Each tablet formulation contained alprazolam, HPMC (Methocel K4MP), excipients, and magnesium stearate. The soluble excipients investigated were lactose monohydrate, sucrose, and dextrose, and the insoluble excipients included dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, and calcium sulfate dihydrate. The similarity factor (f2 factor) was used to compare the dissolution profile of each formulation. The insoluble excipients, especially dicalcium phosphate dihydrate, caused the drug to be released at a slower rate and to a lesser extent than the soluble excipients. Soluble excipients created a more permeable hydrated gel layer for drug release, increased the porosity resulting in faster diffusion of drug, and increased the rate of tablet erosion. Use of binary mixtures of lactose monohydrate and dicalcium phosphate dihydrate produced release profiles of intermediate duration. Rapid drug dissolution was obtained when only 9.1% w/w of lactose monohydrate was present in the tablet formulation. Only when the dicalcium phosphate dihydrate level was sufficiently high (36.5% w/w) was the release rate and extent decreased. It was demonstrated that the type and level of excipient influenced the rate and extent of drug release from controlled release tablets containing HPMC. The release mechanism of alprazolam from each tablet formulation was described by either the Hixson-Crowell cube root kinetics equation or Peppas's equation. However, the different excipient types investigated did not influence the release mechanism of alprazolam from the final tablets.     

均匀设计试验筛选阿替洛尔分散片的处方

目的：筛选阿替洛尔分散片处方。方法：制备阿替洛尔分散片并考察其质量,以微晶纤维素（MCC）、羧甲基纤维素钠（CMS—Na）、硬脂酸镁的用量和乙醇的质量浓度为考察因素,以阿替洛尔分散片30min的体外累积溶出度为指标,采用均匀设计试验筛选处方,验证处方并比较市售普通片和自制分散片45min内的体外累积溶出度。结果：成功制备了阿替洛尔分散片,质量符合分散片的要求。最佳分散片处方为45．0％MCC、7．0％CMS．Na、1．00％硬脂酸镁、40％乙醇溶液,验证试验结果表明处方设计合理。以最优处方制备的阿替洛尔分散片在30min的体外累积溶出度为91．78％,分散片的体外累积溶出度[（93．4±0．9）％]高于市售普通片[（89．0±1．2）％]。结论：研制的阿替洛尔分散片处方合理、工艺简单可行。     

伏立康唑片的制备及其质量评价

目的制备并评价伏立康唑片。方法采用预胶化淀粉、一水乳糖、交联羧甲基纤维素钠、聚维酮、硬脂酸镁制备伏立康唑片,并对其进行薄膜包衣。采用正交设计法确定最佳处方。对其硬度、脆碎度和溶出度进行考察并与市售伏立康唑片比较。结果预胶化淀粉、一水乳糖、交联羧甲基纤维素钠、硬脂酸镁的用量分别为片重的40%,21%,3%和1%,采用5%聚维酮K90水溶液做黏合剂,片芯硬度为15 kg.cm 2,包衣厚度为4%左右时,伏立康唑片的溶出度接近原研产品。结论伏立康唑片的制备工艺简单,重现性好,药物的溶出行为达到预期目的。     

硫酸吗啡口腔崩解片的制备及处方工艺研究

目的:制备硫酸吗啡口腔崩解片,优化其处方工艺条件。方法:采用直接压片法制备硫酸吗啡口腔崩解片,以崩解时间和口感为指标采用单因素试验法筛选片剂硬度、硬脂酸镁用量、甜菊苷用量范围等,再以崩解时限为指标采用星点设计法优化微晶纤维素(SMCC)、交联羧甲基纤维素钠(CCMC-Na)、甜菊苷用量,并对最优处方所制制剂进行验证。结果:最优处方组成为(片质量60 mg):硫酸吗啡16.67%、SMCC 35.77%、CCMC-Na 8.94%、甜菊苷2.85%、硬脂酸镁1%、甘露醇34.77%。所制口腔崩解片硬度为3 kg,能在12 s内完全崩解,且味微甜、口感良好。结论:该制剂制备方法简便、可行。     

Application of external lubrication during the roller compaction of adhesive pharmaceutical formulations

A novel use of external lubrication has been investigated in which magnesium stearate was applied directly to the roll surface during roller compaction. A scalable parameter; travelling roll distance per shot (D_pS), has been defined which ensures that an equal amount of magnesium stearate is applied to the roll surface per rotation at any roll speed. It was found that a formulation containing 20% w/w of either the API Pravastatin or Ibipinabant required a smaller D_pS than a placebo formulation in order to prevent roll adherence. The inherent adhesiveness, and hence the required amount of external magnesium stearate to prevent roll adhesion, will depend on the material properties of the formulation. The amount of magnesium stearate transferred from the roll surface to the ribbon was measured using inductively coupled plasma optical emission spectroscopy and was found to be less than 0.01% w/w. This is a significant reduction in magnesium stearate compared to the normal manufacturing procedure of blending 0.25–2.0% w/w within the formulation.The advantage of external lubrication during roller compaction is the significant reduction in magnesium stearate from the formulation which could lead to the production of tablets with superior mechanical properties and faster dissolution times.     

氯氮平口腔崩解片的研制

目的以氯氮平为模型药物制备口腔崩解片。方法以沉降容积比及崩解时间为指标,单因素法筛选片剂的处方组成及工艺,并优化制备工艺。结果氯氮平口腔崩解片以甘露醇、明胶、阿司帕坦与薄荷香精为辅料,经冷冻干燥法制备,口感良好,崩解时间为5 s,体外溶出度3 m in达94%。结论氯氮平口腔崩解片可迅速崩解于口腔内,制备工艺可行。     

Functionality of magnesium stearate derived from bovine and vegetable sources: dry granulated tablets

Magnesium stearate is a functional excipient used to ensure efficient ejection of tablets. This study compares the functionality of a vegetable and bovine grade of magnesium stearate. Tablets were prepared by direct compression and dry granulation of a model formulation. Physical and chemical tests were performed on bulk powders, granule intermediates, and finished tablets to provide a comprehensive comparison of the two grades of magnesium stearates. Raw material characterization of the two grades showed no difference in particle size, surface area, true density, and total moisture content. However, significant differences in fatty acid composition, surface tension, and zeta potential were detected. Tablet ejection force for the physical mixture formulations was variable, showing similar ejection force for the two grades of magnesium stearate at some concentrations and different ejection forces at other concentrations. The dry granulated formulation containing vegetable-based magnesium stearate showed a lower ejection force than the formulation containing bovine-based magnesium stearate. There was no difference between the dissolution profiles of the tablets containing the two grades of magnesium stearate prepared by both methods. The results indicated that magnesium stearate interchangeability with respect to lubricant efficiency depends upon the level in which it is used and the manufacturing method.     

正交设计优化孟鲁司特钠片的处方工艺

目的:制备孟鲁司特钠片,筛选其最佳处方工艺。方法:采用正交设计法,以与进口孟鲁司特钠片的相似因子f2为指标,对自制孟鲁司特钠片中微晶纤维素与乳糖的比例(A),交联羧甲基纤维素钠(B)、羟丙基纤维素(C)和硬脂酸镁(D)的处方用量百分比进行优选,并进行验证试验。结果:优选所得A、B、C、D分别为41∶45、2.5%、5.5%、0.80%,3批优化处方所制样品f2值均大于50,2种制剂溶出曲线基本相似,30min时累积溶出度均能达到80%以上。结论:自制孟鲁司特钠片处方合理,制备工艺简单易行,体外溶出度良好。     

盐酸伊托必利片的处方筛选及生物等效性研究

目的：筛选确定盐酸伊托必利片的最佳处方,并确定其生物等效性。方法：利用片剂基本性能评价筛选出盐酸伊托必利片合适的处方,再考察体外溶出度,优化出最佳的处方配比。利用其试制药品与参比药品在大鼠体内的药代动力学曲线比较,确定生物等效性。结果：处方确定为盐酸伊托必利50 g,微晶纤维素24 g,乳糖40 g,羧甲淀粉钠7 g,1%羟丙甲纤维素溶液适量,硬脂酸镁0.6 g,制成1000片。试制药与参比药的血药浓度变化趋势基本一致,与参比药品相比具有生物等效性。结论：按照上述处方制成的成品,处方合理,方法简单,便于生产。