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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

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Our research group has pioneered the development of liquisolid pellets as a new drug delivery system targeting at the improvement of the dissolution rates of poorly water-soluble drugs, combining the technological and biopharmaceutical advantages of both multiparticulate and liquisolid systems. Recently, Lam and collaborators claimed the invention of "liqui-pellets" as "the emerging next-generation oral dosage form which stems from liquisolid concept in combination with pelletization technology". However, the concept of liqui-pellet is not novel. As we demonstrate in this commentary, liqui-pellets are the same type of preparation as our previously and extensively reported liquisolid pellets. Liquisolid pellets have been disclosed in a patent application and public peer-reviewed articles covering the concept, preparation and challenges associated with these systems. There are no technical differences that justify excluding our previous reports as the first reports on liquisolid pellets or liqui-pellets. This commentary highlights the similarities between liquisolid pellets and liqui-pellets, focusing on the anteriority of liquisolid pellets as disclosed by our group.

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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.

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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.

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Several studies have shown the potential use of Ilex paraguariensis in developing products with the aim to protect biological systems against oxidative stress-mediated damages. In the same way, technological studies have demonstrated the feasibility of obtaining dry products, by spray-drying process, from aqueous extracts of I. paraguariensis in laboratory. The present work was designed to develop pellets by extrusion/spheronization process, from an I. paraguariensis spray-dried powder. The pellets were characterized with respect to their chemical, physical, and technological properties, and the thermal and the photostability of the main polyphenol constituents were investigated. The pellets exhibited adequate size, shape, and high process yield (78.7%), as well as a good recovery of the total polyphenols (>95%) and a good dissolution in water (89.44 to 100.05%). The polyphenols were stable against light when conditioned in amber glass bottles; unstable against heat when the samples were conditioned either in open glass bottles or in hermetically sealed glass bottles and demonstrated to be hygroscopic and sensible to the temperature, especially when stored in permeable flasks. These findings pointed to the relevance of reducing the residual moisture content of pellets as well as of conditioning them in opaque humidity tight packages under low temperatures. The feasibility of obtaining pellets from an I. paraguariensis spray-dried powder using extrusion/spheronization technique was, for the first time, demonstrated. This finding represents a novelty for the herbal products in both pharmaceutical and food fields.

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The performance of the standardized extrusion-spheronization technique, operational conditions, formulation parameters and storage of the final product over the bioactivity of papain containing pellets has been evaluated to obtain an insight into the potential of the technique for the manufacture of solid protein formulations. The pellets produced were assayed in terms of biological activity - monitored at each operational stage using N-benzoyl-dl-arginine ρ-nitroanilide as a substrate, and according to the physical properties - evaluated by means of size distribution, apparent density and friability. The produced pellets presented adequate physical and mechanical properties. Monitoring biological activity at each production stage revealed that the most critical steps corresponded to drying and storage, with bioactivity decay ranging from 5 to 30% and 5 to 20% for each process. Dry mixing and extrusion did not hold any influence over papain activity, while wet massing decreased the bioactivity by approximately 0-5% and the spheronization 0-2%. The results varied as a function of the experimental conditions and formulation components. In conclusion, the extrusion--spheronization technique was suitable to produce solid multiparticulate dosage forms for papain, considering the possibility to originate pellets with relatively low bioactivity decay. However, weak points of the technique corresponded to the wet massing and drying stages as well as storage.

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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.

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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.

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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.