黑曲霉泡腾片制备工艺优化

该研究采用粉末直接压片法制备黑曲霉（Aspergillus niger）泡腾片,以崩解时限、pH值、发泡量为评价指标,通过单因素试验和正交试验对黑曲霉泡腾片的工艺参数进行优化。结果表明,黑曲霉泡腾片的最佳制备工艺为酒石酸和碳酸氢钠比例1.00∶1.25、崩解剂添加量70%、黑曲霉孢子粉添加量15%、质量分数为10%的聚乙二醇6000乙醇溶液为润滑剂,添加量为3.15 g/mL,质量分数为2.5%为聚乙烯吡咯烷酮乙醇溶液为粘合剂,添加量为7 g/mL。在此优化条件下所得的黑曲霉泡腾片表面光滑,黏冲不明显,pH值为5.7,且崩解时限（23 s）、发泡量（40.79 mL/g）、硬度（4.3 kg）均符合2015版《中国药典》的规定,在水中可迅速崩解。     

Self-Microemulsifying Drug Delivery Systems (SMEDDS) for Improving In Vitro Dissolution and Oral Absorption of Pueraria Lobata Isoflavone

The aim of our investigation was to develop and characterize self-microemulsifying drug delivery systems (SMEDDS) of Pueraria lobata isoflavone to improve its in vitro dissolution and oral absorption in beagle dogs. SMEDDS consisted of oil (ethyl oleate), a surfactant (Tween 80), and a cosurfactant (Transcutol P). In all the SMEDDS, the level of Pueraria lobata isoflavone was fixed at 20% w/w of the vehicle. The in vitro self-microemulsification properties and droplet size analysis of SMEDDS were studied following their addition to water under mild agitation. A pseudoternary phase diagram was constructed identifying the efficient self-microemulsification region. From these investigations, an optimized formulation was selected and its dissolution and bioavailability were compared with a tablet formulation in beagle dogs. The in vitro dissolution rate of puerarin from SMEDDS was more than threefold faster than that from Yufengningxin tablets (Pueraria lobata isoflavone tablets). A 2.5-fold increase in the relative bioavailability was observed for the SMEDDS compared with Yufengningxin tablets. The absolute bioavailability of the SMEDDS was 82.32 ± 15.51%, which was significantly improved compared with that of Yufengningxin tablets. These results demonstrate the potential of SMEDDS as an efficient way of improving the oral absorption of Pueraria lobata isoflavone.     

Release of Cyclobenzaprine Hydrochloride from Osmotically Rupturable Tablets

ABSTRACT

Osmotically rupturable systems were developed and the release of cyclobenzaprine hydrochloride (model drug) from the systems was investigated. Systems were designed using mannitol (osmotic agent) and increasing amounts of polyethylene oxide (PEO, a water-swellable polymer) surrounded by a semipermeable membrane. When placed in an aqueous environment, osmotic water imbibition into the systems distended and swelled the systems until the membrane ruptured and released the active compound to the outside environment. Tablets with increasing amount of PEO exhibited longer rupture times. This may be due to osmotic pressure-modulating properties of the polymer, changing the rate of water imbibition into the systems.

The integrity of the membranes was investigated using high-pressure mercury intrusion porosimetry. Minimal mercury intrusion into the membrane structure and core tablet indicated membrane integrity and lack of defective areas or pinholes. The results were in agreement with the release profiles where no drug release was detected prior to membrane rupture. Mercury intrusion porosimetry appears to be a promising technique for evaluation of membrane integrity.

Once the systems ruptured, drug was released by osmotic pumping and diffusion mechanisms through the ruptured area. There was a decrease in drug release rate with inclusion of PEO in the core.

The effects of film thickness on rupture and release times were also investigated. Devices with thicker films produced longer rupture times. This is in agreement with the theoretical prediction.     

Power of Experimental Design Studies for the Validation of Pharmaceutical Processes: Case Study of a Multilayer Tablet Manufacturing Process

ABSTRACT

Experimental design studies (EDS) are already widely used in the pharmaceutical industry for drug formulation or process optimization. Rare are the situations in which this methodology is applied for validation purposes. The power of this statistical tool, key element of a global validation strategy, is demonstrated for a multilayer tablet manufacturing process. Applied to the Geomatrix® system generally composed of one compression and three granulation processes, time and strictness gains are non-negligible. Experimental design studies are not used in this work for modeling. Introduced at each important step of the process development, they allow for the evaluation of process ruggedness at pilot scale and specifications for full production. A demonstration of the complete control of key process parameters is given, identified throughout preliminary studies.     

Comparison of pharmacokinetics in beagle dogs of nimesulide bilayer tablets with dispersible tablets

The purpose of this study was to compare the in vitro release and the in vivo pharmacokinetics of bilayer tablets with the conventional dispersible tablets of nimesulide. The tablets were administered to beagle dogs and the plasma levels of nimesulide were determined by high-performance liquid chromatography-MS/MS. The pharmacokinetic parameters were calculated using a noncompartmental model. The bilayer tablets showed a biphasic in vitro release pattern with initial burst release and sustained release following the quasi-Fickian diffusion-based release mechanism. The C_max, t_max, mean residence time (MRT), and area under the curve from 0 to 36 h were 10.8 ± 4.2 μg/mL, 2.3 ± 1.0 h, 6.7 ± 2.1 h, 81.5 ± 26.7 μg·h/mL for the bilayer tablets and 14.8 ± 5.8 μg/mL, 2.7 ± 0.8 h, 5.6 ± 0.9 h, 95.4 ± 44.2 μg·h/mL for the dispersible tablets. Compared with the dispersible tablets, the bilayer tablets have lower C_max, similar t_max, and longer MRT. The aforementioned pharmacokinetic parameters, especially the MRT demonstrated to be valuable for evaluating the biphasic characteristics. This study provides a promising in vivo evaluation method for the bilayer tablets with biphasic release pattern.     

Formulation and In Vitro Studies of a Fixed-Dose Combination of a Bilayer Matrix Tablet Containing Metformin HCl as Sustained Release and Glipizide as Immediate Release

The emerging new fixed dose combination of metformin hydrocholride (HCl) as sustained release and glipizide as immediate release were formulated as a bilayer matrix tablet using hydroxy propyl methyl cellulose (HPMC) as the matrix-forming polymer, and the tablets were evaluated via in vitro studies. Three different grades of HPMC (HPMC K 4M, HPMC K 15M, and HPMC K 100M) were used. All tablet formulations yielded quality matrix preparations with satisfactory tableting properties. In vitro release studies were carried out at a phosphate buffer of pH 6.8 with 0.75% sodium lauryl sulphate w/v using the apparatus I (basket) as described in the . The release kinetics of metformin were evaluated using the regression coefficient analysis. There was no significant difference in drug release for different viscosity grade of HPMC with the same concentration. Tablet thus formulated provided sustained release of metformin HCl over a period of 8 hours and glipizide as immediate release.     

Preparation of medicinal carbon tablets by modified wet compression method

Background: Although medicinal carbon (MC) is useful to treat intoxications caused by orally taken toxic chemicals or toxins, high dose of MC is a burden on patients and sticks to oral mucosa or throat. A tablet dosage form of MC is useful to solve such problems. Fast-disintegration, adequate hardness, and quick and high-adsorption potential are required for MC tablets. Method: A modified wet compression method using carboxymethylcellulose sodium (CMC-Na) solution as binder solution was newly developed. Croscarmellose sodium (CC-Na) was used as a disintegration agent. MC granules, binder solution, and MC granules were placed in the cylinder in that order, and the resultant mass was compressed. The obtained tablets were examined for hardness, disintegration rate, and acetaminophen adsorption profiles. Results: The tablets, produced with MC granules containing CMC-Na and CC-Na at 10% each and using 280?μL of 2.5% (w/w) CMC-Na binder solution in compression, showed adequate hardness (more than 4?kg), short disintegration time (less than 6 min), and almost the same acetaminophen adsorption profile as intact MC powder. Conclusion: The modified wet compression with CMC-Na and CC-Na is suggested to be useful to obtain MC tablets with good quality.     

安吉白茶含片的制作及其抗氧化活性评价

经过筛选配方和优化工艺,采用湿颗粒法制备安吉白茶含片并进行质量评价;采用清除DPPH自由基、ABTS+自由基,测定亚铁离子螯合活性和还原力,评价其抗氧化活性。结果表明,安吉白茶提取物、蔗糖、柠檬酸、糊精等对含片的质量有较大影响,最佳配方为90%乙醇做湿润剂,成品含5%安吉白茶提取物、40%蔗糖、20%麦芽糊精、1.6%柠檬酸、3%VC、5%牛磺酸、25.4%甘露醇和0.6%硬脂酸镁。该含片清除DPPH自由基、ABTS+自由基的IC50分别为48.74、43.32μg/mL,对亚铁离子的半螯合浓度为773.60μg/mL,还原力为0.97μmol/mg。该含片口感好,有安吉白茶风味,表面光滑美观,硬度、崩析性好,具有良好的抗氧化活性。     

人参蓝莓口嚼片的研制

精选白参经过超声波提取,得到人参提取物。蓝莓经过榨汁、喷雾干燥制成蓝莓果汁粉。以人参提取物和蓝莓果汁粉为主要原料,淀粉、木糖醇等为辅料,以40%乙醇作为润湿剂,经压片而制成的一种新型口嚼片。通过单因素和正交试验,确定最佳工艺条件和配方。结果表明,人参提取物添加量为15%、蓝莓果汁粉添加量35%、淀粉添加量为20%、40%乙醇添加量为40%。     

Spatially resolved characteristics of pharmaceutical sprays

Spatially resolved drop size, velocity, and volume flux data for five different spray coating guns were described in this study. Such spatially resolved measurements show how sprays respond to changes in operating conditions and gun design in ways that less complete measurements can not provide. Data for instance, allow us to recognize the unique drop size distribution of one of the sprays tested, which ultimately was an important factor in determining the dual roles of the shaping air flows: depending on drop size, viscosity, and the magnitude of the shaping air velocity, the shaping air can either pinch or induce secondary atomization to the sprays. When the former outweighs the latter, a dumbbell‐shaped spray develops; a more uniform spray results when the opposite occurs. Volume flux data from the different sprays also suggest that a more robust and consistent tablet coating process can likely be designed by utilizing multiple overlapping round sprays. © 2011 American Institute of Chemical Engineers AIChE J, 2012