盐酸丁咯地尔缓释片的制备及体外释放度研究

以羟丙甲纤维素和丙烯酸树脂为骨架材料，5％乙基纤维素乙醇溶液作为粘合剂，采用湿法制粒压片，制备盐酸丁各地尔缓释片，进行体外释放度试验，并与进口缓释片进行比较。结果表明：研制缓释片的缓释效果良好，药物的释放符合一级动力学规律。     

布洛芬缓释片的制备及体外释放研究

目的 制备布洛芬缓释片,考察不同因素对药物释放的影响.方法 以羟丙基甲基纤维素(HPMC)为亲水性凝胶骨架材料制备布洛芬缓释片,考察羟丙基甲基纤维素(HPMC)、微晶纤维素(MCC)用量对缓释片释放速率的影响.结果 羟丙基甲基纤维素及微晶纤维素用量对布洛芬缓释片释放具有一定的影响,优化后的处方体外释放符合Higuchi方程.结论 通过调节处方比例,可获得具有满意释放的布洛芬缓释片.     

HPLC法测定布洛伪麻缓释片的释放量

摘 要 目的:建立高效液相色谱法测定布洛伪麻缓释片释放量的方法。方法: 色谱柱为迪马 C₁₈（250 mm×4.6 mm,5 μm）,流动相为甲醇-三乙胺-0.04 mol·L^-1 磷酸二氢钠溶液 (60∶0.02∶40),流速为1.0 ml·min^-1,检测波长为215 nm,柱温为35℃,进样量为20 μl。结果:布洛芬的线性范围为40～2 000 μg·mL^-1（r＝1.000 0）,平均加样回收率为99.2％,RSD＝0.8％(n=9),最低定量浓度为0.04μg· mL^-1;盐酸伪麻黄碱的线性范围为6～300 μg·mL^-1（r＝1.000 0）,平均加样回收率为98.5％,RSD＝0.6％(n=9),最低定量浓度为0.06μg· mL^-1。结论: 该方法简便快速、准确灵敏,可用于布洛伪麻缓释片释放量的测定。     

洛芬葡锌那敏片的质量控制

目的：建立洛芬葡锌那敏片的质量标准。方法：采用HPLC法测定洛芬葡锌那敏片中布洛芬和马来酸氯苯那敏的含量及含量均匀度。结果：马来酸氯苯那敏、布洛芬分别在0．42～8．32μg·ml^-1（r=0．9999）,30．16～603．20μg·ml^-1（r=0．9999）范围内有良好的线性关系,平均回收率分别为101．8％（RSD=1．0％,n=9）,101．6％（RSD=1．1％,n=9）。结论：该方法简便、快速、准确,可以有效地控制药品质量。     

正交设计法优化布洛芬缓释骨架片的处方工艺

目的:制备布洛芬缓释骨架片并筛选其最佳工艺条件。方法:以累积释放百分率为考察指标,以羟丙甲纤维素(HPMC)、微晶纤维素(MCC)处方中用量及片剂的硬度等为考察因素,采用正交试验设计L9(34)进行处方和工艺优化。结果:优化布洛芬缓释骨架片处方工艺中HPMC、MCC处方中用量分别为12.5%、3.0%,片剂硬度为80 N;制备的3批布洛芬缓释骨架片可持续释放24 h,具有明显的缓释效果,其释放符合Higuchi方程(r>0.980 0)。结论:优化的工艺可行,可延长布洛芬的释药时间。     

不同方法制备的控释膜力学与药物渗透性能研究

分别采用平面铸膜法和喷雾法制备游离的Eudragit RS100控释包衣膜，通过张力仪测定了膜力学性能，并以盐酸氨溴索为模型药物测定了膜的渗透性能，以考察两种方法制备的控释膜性能的重现性，试验结果显示两法制备的膜力学性能差异显著，但重现性均符合要求，喷雾法制备的控释膜盐酸氨溴索的渗透速率重现性差而平面铸膜法制备的膜重现性则较好，此外平面铸膜法制备的膜其盐酸氨溴索的渗透速率仅由膜本身控释能力决定，不受搅拌速率，供给池药物浓度变化等因素影响，即实验因素影响小，较适用于薄膜试验。     

The Influence of Thermal Treatment on the Physical-Mechanical and Dissolution Properties of Tablets Containing Poly(DL-Lactic Acid)

Five molecular weight grades of poly(DL-lactic acid) (PLA) were incorporated as organic and aqueous pseudolatex binders into matrix tablet formulations containing microcrystalline cellulose and the model drug theophylline. The tablets were thermally treated to temperatures above and below the glass transition temperature (T _g) of the PLA. The results of the dissolution studies showed that thermally treating the tablets to temperatures above the T _g of the PLA significantly retarded the matrix drug release compared to tablets which were not thermally treated. The retardation in drug release could be attributed to a stronger compact and a more efficient redistribution of polymer throughout the tablet matrix, based on fundamental principles of annealing. In addition, results from tablet index testing supported the dissolution results. The bonding index of the compact formulations increased after thermal treatment above the T _g of the PLA. Gel permeation chromatography and differential scanning calorimetry studies demonstrated that thermal treatment had no significant effect on the molecular weight and the glass transition temperature of (PLA) alone and in combination with other components of the tablet formulation.     

火焰原子吸收法测定洛芬葡锌那敏片中锌的含量

目的 建立火焰原子吸收法测定洛芬葡锌那敏片中Zn的含量。方法 采用火焰原子吸收法,检测波长为213．9nm,灯电流为8．0mA,狭缝宽度为0．5nm,燃气流量为2．0L·min^-1,助燃气流量为15．0L·min^-1。结果 Zn在0．0000-2．0000mg·L。范围内线性关系良好,相关系数为0．9985,平均加样回收率为99．07％（RSD=0．3％,n=9）。结论 该研究可控制洛芬葡锌那敏片中锌的含量,灵敏度高。     

Influence of formulation and process parameters on the release characteristics of ethylcellulose sustained-release mini-matrices produced by hot-melt extrusion

Mini-matrices (multiple unit dosage form) with release-sustaining properties were developed by hot-melt extrusion (cylindrical die: 3 mm) using metoprolol tartrate as model drug and ethylcellulose as sustained-release agent. Dibutyl sebacate was selected as plasticizer and its concentration was optimized to 50% (w/w) of the ethylcellulose concentration. Xanthan gum, a hydrophilic polymer, was added to the formulation to increase drug release. Changing the xanthan gum concentration modified the in vitro drug release: increasing xanthan gum concentrations (1%, 2.5%, 5%, 10% and 20%, w/w) yielded a faster drug release. Zero-order drug release was obtained at 5% (w/w) xanthan gum. Using kneading paddles, smooth extrudates were obtained when processed at 60 °C. At least one mixing zone was required to obtain smooth and homogeneous extrudates. The mixing efficacy and drug release were not affected by the number of mixing zones or their position along the extruder barrel. Raman analysis revealed that metoprolol tartrate was homogeneously distributed in the mini-matrices, independent of screw design and processing conditions. Simultaneously changing the powder feed rate (6–25–50 g/min) and screw speed (30–100–200 rpm) did not alter extrudate quality or dissolution properties.     

Box-Behnken设计-效应面法优选四逆泡腾片干法制粒工艺

目的:优选四逆泡腾片干法制粒工艺。方法:以颗粒得率和颗粒脆碎度为评价指标,以轧轮压力、轧轮转速、浸膏粉含水量为考察因素,采用单因素试验考察各因素对指标的影响程度;采用Box-Behnken设计考察各因素对评价指标总评OD值的影响,并采用效应面法预测、分析、选取最佳工艺。结果:最佳干法制粒工艺为浸膏粉含水量为2.1%,轧轮转速为8.8 Hz,轧轮压力为2.3 MPa。结论:所选工艺稳定、可行、重现性好,可用于四逆泡腾片的制粒。     

离子对-反相高效液相色谱法测定布洛伪麻分散片的溶出度

目的:建立离子对-反相高效液相色谱法(IP-RP HPLC)测定布洛伪麻分散片溶出度的方法.方法:采用溶出度第三法(小杯法),以醋酸盐冲液(pH=7.2)为溶出介质.色谱柱为Kromasil C18柱(4.6 mm × 150 mm,5μm);流动相为醋酸-醋酸钠缓冲液-乙腈(4:6),每1000 mL流动相溶解十二烷基硫酸钠1.0 g;检测波长为257 nm.以外标法测定布洛伪麻分散片溶出液中布洛芬和盐酸伪麻黄碱的浓度,并计算相应时间内的累积溶出百分率.结果:布洛芬和盐酸伪麻黄碱分别在0.15～1.5 mg/mL和0.025～0.25 mg/mL范围内,浓度与峰面积呈良好的线性关系(r=0.999 9和0.999 3),平均回收率分别为100.1%(RSD=0.7%,n=9)和100.6%(RSD=0.8%,n=9).结论:IP-RP HPLC法简便,重现性好.     

Development and characterization of extended release Kollidon SR mini-matrices prepared by hot-melt extrusion

Kollidon^® SR as a drug carrier and two model drugs with two different melting points, ibuprofen and theophylline, were studied by hot-melt extrusion. Powder mixtures containing Kollidon^® SR were extruded using a twin-screw extruder at temperatures 70 and 80 °C for ibuprofen and 80 and 90 °C for theophylline. The glass transition temperature (T_g) and maximum torque were inversely related to ibuprofen concentrations, indicating its plasticizing effect. The results of differential scanning calorimetry (DSC) and X-ray diffraction analysis showed that ibuprofen remained in an amorphous or dissolved state in the extrudates containing drug up to 35%, whereas theophylline was dispersed in the polymer matrix. The increase in amounts of ibuprofen or theophylline in the hot-melt extrudates resulted in the increase in the drug release rates. Theophylline release rate in hot-melt extruded matrices decreased as the extrusion temperature increased. In contrast, a higher processing temperature caused the higher ibuprofen release. This was a clear indication of the plasticizing effect of ibuprofen on Kollidon^® SR and a result from water uptake. Theophylline release rate from hot-melt extrudates decreased with increasing triethyl citrate (TEC) level because of the formation of a denser matrix. By adding of Klucel^® LF as a water-soluble additive to the hot-melt extruded matrices, an increase in ibuprofen and theophylline release rates was obtained.     

Influence of polyethylene glycol/polyethylene oxide on the release characteristics of sustained-release ethylcellulose mini-matrices produced by hot-melt extrusion: in vitro and in vivo evaluations

Mini-matrices with release-sustaining properties were developed by hot-melt extrusion (diameter 3 mm, height 2 mm) using metoprolol tartrate as model drug (30%, w/w) and ethylcellulose as sustained-release agent. Polyethylene glycol or polyethylene oxide was added to the formulation to increase drug release. Changing the hydrophilic polymer concentration (0%, 1%, 2.5%, 5%, 10%, 20% and 70%, w/w) and molecular weight (6000, 100,000, 1,000,000 and 7,000,000) modified the in vitro drug release: increasing concentrations yielded faster drug release (irrespective of molecular weight), whereas the influence of molecular weight depended on concentration. Smooth extrudates were obtained when processed at 40 and 70 °C for polyethylene glycol and polyethylene oxide formulations, respectively. Raman analysis revealed that metoprolol tartrate was homogeneously distributed in the mini-matrices, independent of hydrophilic polymer concentration and molecular weight. Also drug and polymer crystallinity were independent of both parameters. An oral dose of 200 mg metoprolol tartrate was administered to dogs in a randomized order either as immediate-release preparation (Lopresor^® 100), as sustained-release formulation (Slow-Lopresor^® 200 Divitabs^®), or as experimental mini-matrices (varying in hydrophilic polymer concentration). The sustained-release effect of the experimental formulations was limited, and relative bioavailabilities of 66.2% and 148.2% were obtained for 5% and 20% PEO 1,000,000 mini-matrices, respectively.     

UV法及Weibull模型评价复方法莫替丁分散片的溶出特性

目的 :评价复方法莫替丁分散片在不同测定方法下的溶出特性。方法 :采用转篮法及桨法测定复方法莫替丁分散片的体外溶出度 ,溶液吸收度以紫外分光光度法测定 ;实验数据采用Excel软件 ,以Weibull分布模型求算溶出参数并拟合回归直线 ,用t检验进行统计学分析。结果 :采用转篮法及桨法测定本复方法莫替丁分散片的溶出度 ,其td 值分别为 1 30 6 3及 0 7931min ;直线斜率间存在统计学差异 (P <0 0 1)。结论 :本品溶出过程受测定方法影响较大 ,提示本品的体内溶出过程与胃肠运动密切相关。     

Effects of Surfactants on Itraconazole-Hydroxypropyl Methylcellulose Acetate Succinate Solid Dispersion Prepared by Hot Melt Extrusion III: Tableting of Extrudates and Drug Release From Tablets

Hydroxypropyl methylcellulose acetate succinate (HPMCAS) has gained popularity as a carrier for amorphous solid dispersion because of its ability to maintain drugs in supersaturated state after dissolution in aqueous media. In part I and II of this series of articles, we have demonstrated that amorphous solid dispersions containing HPMCAS may be prepared using surfactants as plasticizers to reduce processing temperature (Solanki et al., J Pharm Sci. 2019; 108:1453-65), where surfactants also increase dissolution rate and degree of supersaturation (Solanki et al., J Pharm Sci. 2019; 108: 3063-73). The present investigation was undertaken to develop melt extrudates of itraconazole-HPMCAS and itraconazole-surfactant-HPMCAS mixtures into tablets having tensile strength ≥2 MPa, where poloxamer 407 and d-α-tocopherol polyethylene glycol 1000 succinate were used as surfactants. Milled filaments were sieved to collect <212-μm particles, which were then compressed into tablets with different excipients (silicified microcrystalline cellulose [MCC], Avicel PH-102, dicalcium phosphate, lactose, and Starch 1500). Initial screening of various diluents showed that only silicified MCC and Avicel PH-102 could provide the target tensile strength of ≥2 MPa. Tabletability (tensile strength vs. compaction pressure), compressibility (porosity vs. compaction pressure), and compactibility (tensile strength vs. porosity) were then studied for tablet formulations. The desired tensile strength could be obtained at the diluent level of 50%-70%, where silicified MCC provided better hardness than Avicel PH-102. Tablets disintegrated in <2 min, and drug release from tablets was comparable to that of milled filaments.