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.

A feasible classification method of wet masses to predict pellet formation of powdered herbal slices

The aim of the current study was to explore the correlation between physical properties of wet masses and pellet quality by using powdered herbal slices as model drugs. Wet masses with 100 formulations were prepared by taking 20 kinds of powdered herbal slices as model drugs, microcrystalline cellulose as pelletization aid and five levels of added water as liquid binder. Physical properties of the wet masses such as hardness, adhesiveness, springiness, cohesiveness, chewiness, and resilience were measured by a texture analyzer. Meanwhile, the moisture retention capacities (MRC) of powdered herbal slices and wet masses were determined. Particles were classified after they were produced during spheronization. Principal component analysis, factor analysis and classification analysis were performed on the data. Wet masses could be classified into three groups by taking Ha as the first classification index and Ha/Sp as the second classification index. The correct rate of the classification was 91.00%. If Ha value of wet masses was greater than 15610 g, pellets of type ① would form, otherwise, pellets of type ② or type ③ would form based on Ha/Sp value. Then a classification plot of wet masses was developed to predict pellet formation of powdered herbal slices. Meanwhile, the probable mechanism of pellets formation during spheronisation was concluded in this study, which provided useful information to improve pellet quality

Preparation of Amoxicillin Enteric-coated Tablets and Its in Vitro Release Characteristics / 中国药学杂志

OBJECTIVE: To prepare amoxicillin enteric-coated tablets and study the in vitro release properties. METHODS: The drug-containing pellets were prepared by extrusion-spheronization process. Taking the cumulative release at 15 min as the response value, the optimization test was performed using the common rotation combination design and the optimal formulation was validated. The drug-containing pellets were coated with Eudragit L30D-55 to prepare enteric-coated pellets. The effects of different coating weight gains on the release characteristics of enteric-coated pellets, different amounts of plasticizer on the release characteristics of enteric-coated pellets and tablets, and different hardness of tablets on the release characteristics of enteric-coated tablets were investigated by single factor method. RESULTS: The optimal formulation of the drug-containing pellets determined by response surface analysis method included 5% of croscarmellose sodium, 1.2% of polyoxyethylene 35 castor oil and 1% hydroxypropyl cellulose. The predictive value of the cumulative release at 15 min was close to the measured value. The coating weight gain of Eudragit L30D-55 should be about 20%, the amount of plasticizer should be 30% of solid content of Eudragit L30D-55, and the hardness of tablets was (130 ± 20) N. CONCLUSION: It is reasonable and reliable to optimize the formulation of drug-containing pellets by response surface analysis method. The enteric-coated tablets have good delayed release effect, and this product has the feasibility of industrial production.

Effect of wet mass on dextromethorphan hydrobromide matrix pellets

Dextromethorphan hydrobromide (DM) sustained release matrix pellets containing 10% w/w drug were prepared by an extrusion/spheronization technique. The effect of mixing different concentrations of ethyl cellulose (EC), hydroxypropyl methylcellulpse (HPMC K10), and Carbopol 934 with Avicel PH101 on the rheological properties of pellet wet mass was evaluated using mixer torque rheometry (MTR). The prepared pellets were characterized for size, drug content, and in-vitro DM release rate. The results showed that increasing the concentration of the hydrophobic polymer (EC) with Avicel PH101 decreased wet mass consistency, represented by mass mean line torque. Lower binder ratio was required for optimum wet massing, while mixing with swellable polymers (HPMC and Carbopol) caused a noticeable increase in both mean line torque and binder ratio. Combinations of HPMC and Carbopol at higher concentrations resulted in controlled in vitro release of DM from the prepared pellets. Furthermore, mathematical treatment of the in vitro release data of DM from the prepared pellets showed that all formulations except those containing 5% Carbopol plus 5% HPMC (F10) follow first order release. n values of these formulation were in the range of 0.09-0.40, which support an anomalous non-Fickian release.

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.

Wetting agent dosage screening for traditional Chinese medicine pellet based on torque rheological property / 中国中药杂志

With lubricant and bonding effect simultaneously, wetting agent has direct effect on properties of wet mass and extrudate, thus affecting the forming quality of pellets in extrusion-spheronization process. In this research, 25 representative kinds of traditional Chinese medicine(TCM) were selected as model drugs and 20%, 30% and 40% drug loading were set with MCC as their balling agent. The torque rheological curves were measured to get parameters such as maximum torque (Tmax) and corresponding water addition (WTmax) for these 75 raw materials by a mixer torque rheometer (MTR).The results showed that among 75 representative raw materials, 74 ones could be obtained for spherical pellets under the water addition of WTmax-2. corresponding to the second largest torque in torque rheological curve, suggesting that MTR could be used to select the optimal wetting agent dosage of TCM pellets. So the tedious and expensive pre-production work could be considerably reduced when TCM pellets were prepared.

Preparation and in vitro Drug Release of Loxoprofen Sodium Sustained Release Pellets / 中国药师

Objective:To prepare loxoprofen sodium sustained release pellets, and investigate the in vitro drug release behavior. Methods:Loxoprofen sodium loaded pellets were prepared by extrusion-spheronization technology, and the sustained release pellets were prepared with Eudragit RL 30D and Eudragit RS 30D as the sustained release coating film materials. The drug release behavior of loxoprofen sodium sustained release pellets in vitro was studied. Results:Eudragit RL 30D and Eudragit RS 30D with the ratio of 20 ∶80 was used as the sustained release coating film materials, the coating weight was 20%, the plasticizer content was 10%, and the content of talc was 45%. The in vitro release of loxoprofen sodium from the sustained release pellets was steady and entire in 12 h. Conclusion:The release behavior of loxoprofen sodium sustained release pellets is quite satisfactory. And the preparation technology may be used in the industrial production.

Preparation and in vitro release evaluation of pH-dependent colon targetting pellets of Paridis Rhizoma saponin and Astragali Radix polysaccharide / 中草药

Objective: To prepare pH-dependent Paridis Rhizoma saponin (PRS) and Astragali Radix polysaccharide (ARP) colon targeting pellets for the treatment of colon cancer and finish its in vitro release performance evaluation. Methods: The colon targeted pellets were prepared with extrusion-spheronization and air-flow coating method and the the process parameters were optimized by orthogonal design. The coating fluid prescription was investigated by single factor test. In vitro release performance evaluation of the pellets was evaluated with polyphyllin I and II as the indexes. Results: The optimum technologic parameters of extrusion spheronization equipment were as follows: the rate of extrusion was 60 r/min, the rate of spheronization was 1 200 r/min, and the time of spheronization was 5 min. The optimum coating liquid formulation of pH-dependent colon targetting pellets was 15% weight gains of Eudrugit S100, 1.5% anti-plastering aid amount of Glycerin monostearate, and 5% plasticizer amount of TEC. In vitro release test showed that cumulative release rate of berberine hydrochloride was close to 0% in artificial gastric juice after 2 h and less than 10% in artificial intestinal fluid after 4 h, but the cumulative release rate in artificial colon juice after 2 h was more than 90%. Conclusion: The preparation method can be applied to the preparation of colon targeted pellets and the pellets can achieve the targeted release in the colon.

Correlations between physical properties of raw materials and formability of Panax notoginseng saponins pellets / 中草药

Objective: To investigate the correlations between raw material powders, wetting mass and the formability of Panax notoginseng saponins (PNS) pellets. Methods: PNS powder mixed with different proportions of microcrystalline cellulose (MCC), lactose, and starch were made into the pellets by extrusion-spheronization. Particle size, span, density, compressibility, Hausner ratio, specific surface area, pore volume, hygroscopicity, critical relative moisture, and angle of repose were used to evaluate the properties of mixing powders. Liquid solid ratio, plasticity index, liquid point, plastic point, and consistence were used to evaluate the properties of wetting mass. Feret diameter, aspect ratio, yield, density, and friability were used to evaluate the properties of the PNS Pellets. The correlations between the raw materials and the formability of their pellets were analyzed by cluster analysis, principal component analysis, and partial least squares regression analysis. Results: The properties of PNS pellets had no direct correlation with the properties of material powders; The liquid solid ratio, liquid points were positively correlated with the pore volume of powders and were negatively correlated with density, diffusion rate, and span of material powders; The density of the pellets was positively correlated with water content of wetting mass; The dissolution rate was positively correlated with PV and was negatively correlated with the constant ka. Conclusion: There are certain correlations between the formability of PNS Pellets and the physical properties of raw materials.

Application of k-carrageenan in valsartan immediate-release pellets by extrusion-spheronization / 中国药科大学学报

@#The aim of the study was to select a suitable pelletisation aid of valsartan immediate-release pellets in the extrusion process and optimized the formulation. The properties of the pellets with five excipients which were microcrystalline cellulose(MCC), low-substituted hydroxypropyl cellulose(L-HPC), crospovidone(PVPP), pregelatinized starch(PCS)and k-carrageenan were evaluated and compared by the single factor test. And the pelletisation aids were chosen preliminary. The properties of the pellets with MCC, L-HPC, k-carrageenan respectively were evaluated and compared and k-carrageenan was determined as the most appropriate pelletisation aid. The Box-Behnken design was employed to optimize the formulation. The optimised formulation was k-carrageenan 16. 98 g, HPMC-E5 2. 03 g, SLS 0. 26 g. The yield and aspect ratio of pellets was 91. 23% and 1. 14, respectively. And there was no significant difference between observed and predictive responses. The results showed k-carrageenan pellets owned properties of a high yield, acceptable sphericity and fast drug release.

Preparation of Nifedipine Sustained-Release Pellet Tablets and Study of Its Release Behavior in vitro / 医药导报

Objective To prepare nifedipine( NF)sustained-release pellet tablets,and study of its release behavior in vitro. Methods Soluplus was selected as a carrier to prepare solid dispersion of NF by hot melt extrusion technique( HME), and the ratio of the drug to carrier was 1:1. The samples were validated as the solid dispersion by differential scanning calorimetry(DSC). Extrusion-spheronization technique was introduced to prepare NF pellets and EudragitRS 30D was used as the coating material. The NF sustained-release tablets were prepared by direct compression of the coated pellets and suitable excipients. Results The release data in vitro proved that the drug release from the tablets was steady and complete over 24 hours. Conclusion The release of NF from sustained-release tablets is slow and steady. The method is easy to operate. The in vitro drug release pattern follows first-order kinetics.

Preparation of pellets containing Pothomorphe umbellata extracts by extrusion-spheronization: improvement of 4-nerolidylcatechol photostability

Pothomorphe umbellata (L.) Miq., Piperaceae, has been extensively used in Brazilian folk medicine and it is well known for its strong antioxidant properties. However, its main active constituent, 4-nerolydilcatechol (4-NC), is sensitive to ultraviolet and visible light, which can limit the use of intermediate and final herbal preparations of this species. In the present work, coated multiparticulate solid dosage forms of P. umbellata were obtained with the purpose of increasing the stability of 4-NC. P. umbellata extract was used as a wetting liquid for the preparation of pellets by extrusion-spheronization. Pellets were coated in a fluidized bed by three different polymers (hydroxypropylmethylcellulose (HPMC), polyvynilpirrolidone K-30 (PVP-K30), and polyvinyl alcohol-polyethylene glycol graft-copolymer (PVAPEG)). 4-NC photostability was evaluated by an accelerated photostability protocol. Pellets showed a narrow size distribution and low friability. 4-NC photodegradation followed a second order degradation kinetics with similar k values for the percolate, uncoated pellets and HPMC coated pellets. Photoprotection was higher in pellets coated with PVP-K30 and PVA-PEG. PVA-PEG coated pellets with 6 and 9% weight gain resulted in a final concentration of 4-NC approximately cinco times higher than uncoated pellets or liquid extracts, suggesting the potential of this formulation as a multiparticulate solid dosage form for P. umbellata extracts.

Technological development of Cecropia glaziovi extract pellets by extrusion-spheronization

Cecropia glaziovi Snethl., Urticaceae, is commonly used in South America and is one of the species included in the Brazilian Medicinal Plants Research Program. Pharmacological studies have led to reports of the potential of C. glaziovi as a hypotensive, antiasthmatic and anxiolytic agent. The strict requirements regarding the quality, safety and effectiveness of phytopharmaceutical products represent an enormous challenge in the search for products with a high level of uniformity, reproducibility and stability. The incorporation of dry extracts into multiparticulate dosage forms, such as pellets produced by extrusion/spheronization technology, is a suitable alternative to overcome the lack of technological properties of dry extracts, since they are associated with low flowability and high hygroscopicity. In this study, an optimized dry extract (ODE) of C. glaziovi was incorporated into pellets seeking to decrease the moisture sorption and increase the stability, safety and percentage of the extract in the final product. Pellets containing around 50% of ODE were considered the most technologically viable, offering a narrow particle size distribution, significant improvement in the flowability and compressibility properties, and decrease in the moisture compared with the ODE. In conclusion, pellets containing a high dose of the C. glaviovi extract were successfully prepared, achieving degrees of quality, physical stability and feasibility compatible with the desirable characteristics of a phytopharmaceutical.

Preparation of pellets containing highly soluble drug by extrusion/spheronisation and coating with Kollicoat® SR 30D

The aim of this study was to prepare and evaluate the pellets, containing a highly soluble drug (ascorbic acid), by the extrusion-spheronization process and coated with a release controlling polymer. The coating (undertaken in a fluid bed) was applied to three batches of the pellets with a dispersion of Kollicoat® SR 30 D, with each batch of pellets receiving a different level of polymer (5.07; 8.26 and 10.35 percent). The coated pellets were evaluated for sphericity by imaging analysis and comparative dissolution profile with a product commercially available in Brazil. All of the evaluated samples presented adequate physical properties and the dissolution profile of those coated with 5.07 percent of polymer proved to be similar to that of the commercially available brand name.

Preparation and Properties of Oxymatrine Pellets / 中国药房

OBJECTIVE:To prepare oxymatrine pellets and study the pellets' properties.METHODS:Oxymatrine pellets were prepared using an experimental low-temperature extrusion-spheronization granulator.L9(34)orthogonal design was used to obtain optimal formulation.The micromeritic properties and in vitro dissolution of the pellets at different dosage were determined.RESULTS:Oxymatrine pellets prepared by extrusion-spheronization were round and smooth and well-distributed.The optimal technical conditions were as follows:water∶MCC=0.90∶1;spheronization velocity=35 Hz;spheroniza-tion time=5 min;extrusion velocity=40 Hz.The in vitro dissolution was more than 75% within 30 minutes.CONCLUSION:The process of preparing pellets by extrusion-spheronization was simple and feasible and the quality of pellets was excellent.

Study on the Preparation of Lingqiao Jiedu Pellets / 中国中医药信息杂志

Objective To prepare Lingqiao Jiedu Pellets. Methods Lingqiao Jiedu Pellets was prepared by extrusion-spheronization method. Formulation composition and process factors influencing physical properties, such as spherical shape degree and productivity, were optimized. And it had a film coating by fluidized bed. Results Blend the extraction with MCC, and add adequate water. And squeeze with 30 r/min and roll 6 min with the rate of 48 Hz, drying and screening. Conclusion The pellets had a good appearance and stable quality.

Preparation and formulation optimization of Breviscapin Sustained-release Pellets / 中草药

Object To investigate the preparation technique and optimal formulation of Breviscapin Sustained release Pellets (BSP) and the release mechanism of breviscapin from the pellets. Methods BSP was prepared by extrusion spheronization method. Based on the studies of influential factors, optimal formulation modified to release drug over 12 h was obtained by the orthogonal design. And release mechanism of breviscapin from BSP was established by equation fitting. Results Prepared BSP has such advantages as simple technique, uniformity in diameters and high loading with even contents. They can release drug for 12 h. And the release of breviscapin could be mainly controlled by diffusion associated with slight erosion. Conclusion Extrusion spheronization method is simple for the preparation of BSP, and useful for the large scale prodution.

Simultaneous release of index components in Gegen Qinlian Pellets / 中草药

Objective To obtain the same release rate of four index components with significant difference of physicochemical characters,puerarin,baicalin berberine and glycyrrhizin in Gegen Qinlian Pellets.Methods Studies on improving the release rate of less soluble components in Gegen Qinlian Pellets were carried out and the parameters were optimized.The release profiles were analyzed by simulating factor(f_2).Results The f_2 values for baicalin,berberine and glycyrrhizin vs puerarin were 52.27,56.13,and 75.1,respectively.Conclusion The result shows that the same release rate of four index components in Gegen Qinlian Pellets is obtained.

Preparation of Gegen Qinlian Pellets by extrusion-spheronization method / 中草药

Objective To prepare Gegen Qinlian Pellets with higher yield of drug loading and being good for industrial production.Methods The Gegen Qinlian Pellets were prepared by extrusion-spheronization.The effects of four key parameters on spheronization process were the proportion of bond,extrusion speed,spheronisation speed,and spheronisation time,which were investigated to obtain optimal formulation.Results Gegen Qinlian Pellets presented perfect sphericity and narrow diameter distribution.Drug loading in the pellets could be up to 70% and yelid over 90%.Conclusion The Gegen Qinlian Pellets are successfully prepared by extrusion-spheronization.It presents a method for industria-lized production of Chinese materia medica.

Formula and process optimization of Danggui Buxue Pellets prepared by extrusion-spheronization / 中成药

AIM: To prepare traditional Chinese medicine formula Danggui Buxue Pellets by extrusion-spheronization and to study the optimal process and formulation. METHODS: Danggui Buxue Pellets were prepared by a new style extrusion-spheronization equipment;The optimal process and formulation were obtained on the studies of influenitial factors and L_9(3~4) orthogonal design,The micromeritic properties and reception percentage of pellets were determined. RESULTS: The prepared Danggui Buxue Pellets by extrusion-spheronization were all spheral with smooth surface;The percent of reception was not less than 85%. CONCLUSIONS: Extrusion-spheronization is suitable to produce herbal medicine pellets.The preparation process is simple and feasible;The quality of the prepared pellets is excellent and the percent of reception is high.