Preparation and in-vitro drug release of Baizhu Huanglian pellets containing colon-targeting capsules / 药学实践杂志

Objective Colon-targeting capsules based on gastric pellets and enteric pellets were prepared from Baizhu Huanglian prescription. The formulation composition and preparation process were optimized and the in-vitro release characteristics were investigated. Methods Optimum formulation composition and process parameters of Baizhu Huanglian pellets were screened out by single factor experiment and orthogonal design. The pellets core were prepared by extrusion-spheronization technique and coated in the fluid bed using bottom spray coating technique. To investigate the effect of coating level of the isolation layer, the proportion of polymer, the amount of plasticizer and weight gain of enteric coating on the release behavior of the enteric pellets. The pellets release behavior was fitted by model as well. Results The prescription of gastric pellets was drug loading 50%, PVPP 5%, MCC to lactose 1∶2 and wetting agent 40%. The process parameters were extrusion frequency 20 Hz, rounding speed 500 r/min and rounding time 5 min. The prescription of enteric pellets was drug loading 27%, PVPP 5%, MCC to lactose 5∶2, wetting agent 30% and adhesive 20%. The process parameters were extrusion frequency 20 Hz, rounding speed 700 r/min and rounding time 7 min. For enteric coating layer, the coating mixture of EUDRAGIT®L30D-55 to EUDRAGIT® FS30D was 1∶2. The amount of plasticizer was 10%. The increased weight of coating layer was 15%. The release time of enteric pellets in-vitro was up to 24 hours. The release behavior of the pellets conforms to the Higuchi model. Conclusion The colon targeting capsule of Baizhu Huanglian pellets were successfully prepared and showed the characteristics of sustained release and colon targeting.

Improving compactibility properties of Lonicera Japonica Flos by Plasdone S-630 / 药学学报

To improve the fluidity and compactibility properties of raw powders of traditional Chinese medicine by particle modification technology, Lonicera Japonica Flos was used as a model drug, fluidized bed bottom spray technology was used, and Plasdone S-630 was used as a modifier to prepare modified particles. The powder properties, tablet compactibility parameters, disintegration time and dissolution were measured. The surface morphology of the powder particles before and after modification and compressed tablets were characterized by combining with scanning electron microscopy technology. The results showed that the particle size of Lonicera Japonica powder has been increased after particle modification, the fluidity, compressibility and compactibility of the powder have been improved to some extent, the disintegration time has also been reduced, and the dissolution in vitro is not affected. Therefore, this study can provide reference and ideas for the common problem that raw powder of traditional Chinese medicine that cannot meet the needs of preparation production due to poor powder properties such as fluidity and compressibility.

Improvement on the tableting properties of traditional Chinese medicine extracts by fluid-bed coating and pore forming / 药学学报

This paper aimed to study the effect of combined co-processing of coating and pore forming on the tableting and tablet properties of traditional Chinese medicine (TCM) extracts together with its applicability. Four TCM extracts were co-processed using fluid bed with hydroxypropyl methyl cellulose (HPMC) as coating agent and ammonium bicarbonate (NH4HCO3) as pore-forming agent. Powder properties (such as particle size and size distribution, bulk density, tap density, moisture content) and tablet properties (including tensile strength, compaction ratio, fast elastic stretch, and disintegration time) were measured and compared among the powders. Scanning electron microscopy (SEM) was applied to characterize the surface of particles and tablets. Results showed that the particle size, flowability, and compactibility of the composite particles with HPMC were superior to the parent powders of TCM extracts. These properties of the porous particles with HPMC and NH4HCO3 showed further improvements. In addition, the addition of HPMC prolonged the disintegration time of tablets, whereas the pore-forming effect of NH4HCO3 could shorten the disintegration time. SEM revealed the changes in the morphology of the composite particles and the pores on the surface of the porous particles and tablets. In conclusion, co-processing with HPMC and NH4HCO3 could improve the powder and tablet properties of TCM extract powders, and this method shows certain applicability, which provides a feasible choice for improving the tableting properties of some TCM extract powders.

Formulation development and evaluation of colon targeted delayed release methotrexate pellets for the treatment of colonic carcinoma

Colonic carcinoma is one of the most common internal malignancies and is the second leading cause of deaths in United States. Methotrexate (MTX) is a drug of choice in the treatment of colon cancer. The aim of the present research work was to develop and characterize colon targeted pellets of MTX for treatment of colonic carcinoma. The product and process parameters were optimized by screening methods. Pellets were prepared by extrusion spheronization using microcrystalline cellulose (MCC) as spheronizing aid and ethyl cellulose (EC) as release retardant in different ratio. Based on the physical appearance, sphericity and % in vitro drug release, batch P17 containing EC: MCC (3:7) was optimized for core pellets. The site specificity was obtained by screening the coating polymers and by coating the core pellets with EudragitS100. The 32 full factorial design was applied in which airflow rate (X1) and coating time (X2) were the independent parameters and physical appearance (Y1) and time taken for 100% drug release (Y2) were selected as the dependent variables. From the results obtained, 6min of coating time and 60cm3/min airflow rate was optimized. The batch B5 showed appropriate physical appearance and % in vitro drug release upto 17hr indicating sustained release property. The ex-vivo studies performed on rat colon indicated a significant relation with the in vitro drug release. The drug release followed Higuchi's model indicating the diffusion pattern of drug release from the matrix of pellets. Thus, the coated pellets can be a good candidate for site specific delivery of MTX to colon by decreasing the gastric irritation and thus to improve bioavailability.

Investigation of formulation, preparation and stability of rosuvastatin calcium tablets / 第二军医大学学报

Objective To explore the formulation and preparation technique of rosuvastatin calcium tablets with satisfactory stability and reproducibility. Methods Using suitable formulations, we prepared the rosuvastatin calcium granulates by high shear mixer and fluid bed separately, and compared their influences on the granulate properties, tablet characteristics and dissolution. The reproducibility of formulation and preparation technique was investigated. Furthermore, the factors affecting the formulation were also investigated. Results Compared with the fluid bed, granulation using high sheer mixer was more suitable for preparing rosuvastatin calcium granulates. The selected formulation and preparation technique yielded 3 batches of rosuvastatin calcium tablets which met the quality requirement. The tablets had a comparable dissolution profiles to "Crestor " of AstraZeneca. The stability of rosuvastatin calcium was largely affected by the strong light, high humidity and high temperature. Conclusion The optimized formulation and preparation technique have good reproducibility for preparing rosuvastatin calcium tablets, which have good stability.

Preparation of esomeprazole magnesium enteric-coated capsules / 中国药学杂志

OBJECTIVE: To prepare and evaluate esomeprazole magnesium enteric-coated capsules which is compacted by multiple-unit pellet system (MUPS). METHODS: The esomeprazole magnesium enteric-coated pellets were prepared by fluid bed coating technology, and the effects of isolation layer, amont of core, and thickness of enteric-coated film on the quality of the product were e-valuated. RESULTS: The prepared esomeprazole magnesium enteric-coated capsules showed good release behavior in artificial gastric fluid. The dissolution in artificial intestinal fluid was rapid and complete. CONCLUSION: The established process of preparing esomeprazole magnesium enteric-coated pellets is feasible and reproducible, and the product has similar quality with the original preparation. It is expected to be used in the industrial production.

Formulation and evaluation of esomeprazole magnesium dihydrate multiple unit particulate system ( pellets) as a delayed release dosage form.

The present study was an attempt to formulate and evaluate enteric coated tablets for Esomeprazole magnesium dihydrate delayed release multiparticulate to reduce the Gastrointestinal tract side effects.The delayed release multiple units were prepared by using fluid-bed werster technology.These multiple units are selected by seal coating, drug coating and enteric coating.These Esomeprazole magnesium dehydrate were evaluated for assay, acid resistence, drug release,dissolution, Kinetic studies of Innovator and Optimized formulation, Stability studies of Optimized formulation. This study concluded Esomeprazole magnesium dihydrate can be prepared by using combination of polymers studied and we can reduce the GI tract side effects.

Characterization and evaluation in vivo of baicalin-nanocrystals prepared by an ultrasonic-homogenization-fluid bed drying method / 中国天然药物

AIM@#To improve the absorption and bioavailability of baicalin using a nanocrystal (or nanosuspension) drug delivery system.@*METHODS@#A tandem, ultrasonic-homogenization-fluid bed drying technology was applied to prepare baicalin-nanocrystal dried powders, and the physicochemical properties of baicalin-nanocrystals were characterized by scanning electron microscopy, photon correlation spectroscopy, powder X-ray diffraction, physical stability, and solubility experiments. Furthermore, in situ intestine single-pass perfusion experiments and pharmacokinetics in rats were performed to make a comparison between the microcrystals of baicalin and pure baicalin in their absorption properties and bioavailability in vivo.@*RESULTS@#The mean particle size of baicalin-nanocrystals was 236 nm, with a polydispersity index of 0.173, and a zeta potential value of -34.8 mV, which provided a guarantee for the stability of the reconstituted nanosuspension. X-Ray diffraction results indicated that the crystallinity of baicalin was decreased through the ultrasonic-homogenization process. Physical stability experiments showed that the prepared baicalin-nanocrystals were sufficiently stable. It was shown that the solubility of baicalin in the form of nanocrystals, at 495 μg·mL(-1), was much higher than the baicalin-microcrystals and the physical mixture (135 and 86.4 μg·mL(-1), respectively). In situ intestine perfusion experiments demonstrated a clear advantage in the dissolution and absorption characteristics for baicalin-nanocrystals compared to the other formulations. In addition, after oral administration to rats, the particle size decrease from the micron to nanometer range exhibited much higher in vivo bioavailability (with the AUC(0-t) value of 206.96 ± 21.23 and 127.95 ± 14.41 mg·L(-1)·h(-1), respectively).@*CONCLUSION@#The nanocrystal drug delivery system using an ultrasonic-homogenization-fluid bed drying process is able to improve the absorption and in vivo bioavailability of baicalin, compared with pure baicalin coarse powder and micronized baicalin.

Drug layering process of model drugs with different dose and solubility / 中国药学杂志

OBJECTIVE: To study drug layering process of model drugs with different dose and solubility.

Preparation and in vtro Release of Dexketoprofen Enteric-coated Pellets / 中国药师

Objective:To prepare dexketoprofen enteric-coated pellets and explore the drug release rate respectively in 0. 1 mol· L-1 hydrochloric acid and phosphate buffered saline(PBS,pH 6. 8). Methods:Dexketoprofen enteric-coated pellets were prepared u-sing fluid-bed coating technology, the blank sugar pellets were coated with drug layer, isolation layer and enteric layer in order. Drug-loading rate as the index, the optimal concentrations of HPMC and drug were screened. Such indicators as adhesion, pellet uniform and surface color as the indices, the coating process was optimized by orthogonal experiment. Drug release in PBS of the enteric-coated pel-lets and the common enteric-coated tablets were compared. Results:The prepared pellets showed the properties of uniform drug load-ing, high drug-loading rate, complete round shape and lustrous appearance. The concentration of HPMC and drug was 5% and 15%, respectively. The optimal coating process was as follows:the material temperature was 36℃, the atomization pressure was 1. 0 bar and the airbrush rate was 0. 8 ml·min-1 . The drug release of the pellets in hydrochloric acid was below 10% in 2 hours, while the release in PBS was greater than that of the common enteric-coated tablets. Conclusion: The prepared enteric-coated pellets are feasible in technology, and exhibit satisfactory acid endurance and drug release in vitro.

Using fluid bed granulation to improve the dissolution of poorly water-soluble drugs

In this study, fluid bed granulation was applied to improve the dissolution of nimodipine and spironolactone, two very poorly water-soluble drugs. Granules were obtained with different amounts of sodium dodecyl sulfate and croscarmellose sodium and then compressed into tablets. The dissolution behavior of the tablets was studied by comparing their dissolution profiles and dissolution efficiency with those obtained from physical mixtures of the drug and excipients subjected to similar conditions. Statistical analysis of the results demonstrated that the fluid bed granulation process improves the dissolution efficiency of both nimodipine and spironolactone tablets. The addition of either the surfactant or the disintegrant employed in the study proved to have a lower impact on this improvement in dissolution than the fluid bed granulation process.

Study on preparation technique of enteric coating Potassium Sodium Dehydroandroan Drographolide Succinate pellets / 中国生化药物杂志

Purpose To build up the Potassium Sodium Dehydroandroan Drographolide Succinate enteric coating sustained-release pellets delivery system by aqueous dispersion coating technique. Methods 1. Adopting MCC as vehicle, SiO_2 as antisticking agent, appropriate amount of 40% ethanol, preparing the core of pellets by extrude-spheronization method and the formulation and manufacturing process were optimized by orthogonal design. 2. Preparing the coating material with Eudragit L 30 D, which is used as pore-forming agent, EC as blocker and PEG6000 as plasticizer. The pellets were coated by fluid-bed coating method. Results 1. The optimal formulation and manufacturing process of pelltes' core were as follows: drug: MCC: SiO_2 = 7:7:5, extruding rate: 1 080 r/min, rounding rate: 960 r/min, rounding time: 5 min. 2. After the addition of EC: Eudragit L = 35:65, the plasticizer is 1.71 % and weight gain is 5% . The release in the gastric model fluid(pH 1.0) < 10% , and complete release ( > 80% ) in the enteric model fluid(pH 6.8) was in two hours. The release behavior accords with the regulations on the release rate of enteric preparation in ChP. Conclusion By adjusting the formulation and the parameters of the process of pellet and coating, we can make enteric coating Potassium Sodium Dehydroandroan Drographolide Succinate sustained-release pellets. All this accords with the regulation of pharmacopedia in vitro release.

Preparation and release characteristics of sodium ferulate sustained-release pellets / 中成药

AIM: To prepare the sodium ferulate sustained-release pellets and evaluate its release characteristics and release mechanism in vitro. METHODS: Sugar core beads and drug-containing pellets were prepared by centrifugal granulation,and then coated by Surelease using the fluid-bed.The release characteristics and release mechanism of the pellets were studied by the dissolution method. RESULTS: The surface of the coated pellets was smooth and glossy and round.The release rate of sodium ferulate met lot-to-lot uniformity.The release rate of the pellet consisted of two kinds of pellets decreased with the increasing of the film thickness.The finishing time was 24 h.The dissolution profiles of sodium ferulate from the pellets showed a good fit of the Higuchi equation.(CONCLUSION): The pellets exhibit more ideal sustained-release characteristics in vitro.

Preparation of Lansoprazole Enteric-coated Pellet Capsules / 中国药房

OBJECTIVE:To prepare lansoprazole enteric-coated pellet capsules(LECPC).METHODS:The lansoprazole enteric-coated pellets were prepared using fluid-bed coating technology through blank pellets being coated with main component layer,insulating layer and enteric layer in order.Enteric-coated pellets were encapsulated into hard gelatin capsules to obtain LECPC.Drug-loading rate and drug release in artificial intestinal fluid and artificial gastric fluid of 3 batches were investigated.RESULTS:The prepared pellets assumed complete round shape,lustrous appearance and coating well with mean drug-loading rate above 96%.The release of 3 batches in artificial intestinal fluid within 45 minutes were greater than (94.3?0.76) % while were smaller than (6.2?1.6)% in artificial gastric fluid within 2 hours.CONCLUSION:The prepared capsule is feasible in technology,reproducible and reliable in quality.It represents satisfactory release in vitro and property of resisting acid.