Study of Load Capacity of Avicel PH-200 and Cellactose,Two Direct Compression Excipients,Using Experimental Design

The load capacity of two excipients, a large particle size grade of microcrystalline cellulose (Avicel? PH-200) and a coprocessed material composed of lactose and pulverized cellulose (Cellactose?) was determined using a model mix with Dipyrone (metamizol sodium) and experiments planned by design of experiments. A multiple-regression model was proposed, and as a result, a new parameter, called specific load capacity S_LC was obtained. This constant can be determined for other excipients and drugs; it depends only on the excipient and the drug used.     

Study of load capacity of Avicel PH-200 and Cellactose, two direct compression excipients, using experimental design

The load capacity of two excipients, a large particle size grade of microcrystalline cellulose (Avicel™ PH-200) and a coprocessed material composed of lactose and pulverized cellulose (Cellactose™) was determined using a model mix with Dipyrone (metamizol sodium) and experiments planned by design of experiments. A multiple-regression model was proposed, and as a result, a new parameter, called specific load capacity S_LC was obtained. This constant can be determined for other excipients and drugs; it depends only on the excipient and the drug used.     

The stress stability of olanzapine: studies of interactions with excipients in solid state pharmaceutical formulations

Stress stability testing represents an important part of the drug development process. It is used as an important tool for the identification of degradation products and degradation pathways, as well as for the assessment of changes in physical form of drug molecules. The impact of excipients on the stability of olanzapine confirms that levels of impurities and degradants are limiting parameters and are therefore used for stability evaluation. The major degradation product of olanzapine was identified as 2-methyl-5,10-dihydro-4H-thieno[2,3-b][1,5]benzodiazepine-4-one (III). The structure of III was determined by using LC-MS, IR and NMR. Compatibility and stress stability results demonstrated that tablet formulations of olanzapine are sensitive to temperature and moisture. In samples protected from moisture, the increase in concentration of III was shown to be highly temperature dependent and the degradation followed zero-order kinetics. In addition, studies of olanzapine with excipients and in formulated tablets revealed polymorphic phase changes in some samples, influenced by a combination of stress temperature and humidity conditions. Polymorphic transitions were monitored using x-ray powder diffraction (XRPD) analysis and exhibited no correlation between the phase change (appearance of a new polymorph) and the degradation process.     

The influence of formulation on the dissolution profile of diclofenac sodium tablets

In attempts to design delayed-release tablets of diclofenac sodium, seven experimental batches were produced. The influence of super-disintegrant croscarmellose sodium (CCS), the granulation process, and the thickness of Eudragit® L 100 coating film were evaluated. The values of dissolution efficiency and the similarity factor were used to compare the dissolution profiles of each experimental batch and the reference Voltaren®. Both methods appear to be applicable and useful in comparing dissolution profiles. Based on such values four batches were considered similar when contrasted with the reference. The results suggest an optimal relationship between the amount of CCS and the thickness of the coating film, which provides appropriate dissolution rate of diclofenac sodium from the dosage forms.     

The Influence of Formulation on the Dissolution Profile of Diclofenac Sodium Tablets

ABSTRACT

In attempts to design delayed-release tablets of diclofenac sodium, seven experimental batches were produced. The influence of super-disintegrant croscarmellose sodium (CCS), the granulation process, and the thickness of Eudragit® L 100 coating film were evaluated. The values of dissolution efficiency and the similarity factor were used to compare the dissolution profiles of each experimental batch and the reference Voltaren®. Both methods appear to be applicable and useful in comparing dissolution profiles. Based on such values four batches were considered similar when contrasted with the reference. The results suggest an optimal relationship between the amount of CCS and the thickness of the coating film, which provides appropriate dissolution rate of diclofenac sodium from the dosage forms.     

Pharmaceutical design of a new lactose-free coprocessed excipient: application of hydrochlorothiazide as a low solubility drug model

Most co-processed excipients used in direct-compression tablets contain lactose, which prevents lactose-intolerant patients from taking such tablets. Therefore, a novel lactose-free co-processed excipient for direct compression tablets has been prepared. Microcrystalline cellulose and dicalcium phosphate dehydrate were used as primary excipients which underwent a wet granulation process and factorial experiment in order to ascertain the best prototype. Finally, the best two prototypes were added to hydrochlorothiazide, which has chosen as the model drug because of its low solubility. An extensive characterization of the new excipient as well as the drug loaded tablets is reported. Our results show adequate parameters (rheological and compression behavior, uniformity of weight, disintegration, friability, crushing force and cohesion index). Moreover, the biopharmaceutical profile was evaluated; the tablets exhibits a Weibull kinetic function and fast drug release.     

Surrogate functionality of celluloses as tablet excipients

Background: The variety of excipients from different sources and prices to which we have access gives rise to the necessity to evaluate their functional characteristics. The aim of this work is to determine some physical and technological characteristics of celluloses from different sources, India and United States, to ascertain their functionality as tablet excipients. Methods: The used surrogate functionality properties are particle morphology and particle size distribution, compactibility, ejection pressure, and the disintegration properties of pure excipients and their compressed tablets. Results: The innovators Avicel and Croscarmellose show advantages over the generic celluloses Alfacel and Carmacel. Avicel PH 101 and 102 show an average of 26% greater compactibility than both types of Alfacel, whereas the compactibility of Croscarmellose is greater than that of Carmacel in about 50%. Avicel tablets compacted at a compaction pressure of 47 MPa exhibit shorter disintegration times (3.7 minutes) than Alfacel tablets (28 minutes), whereas Carmacel show better disintegrant properties than Croscarmellose. This occurs regardless of the similar particle morphology, size, and size distribution. As expected, all celluloses show low ejection pressures. Conclusion: The surrogate functionality properties of the generic celluloses are still considered as satisfactory to be used as tablet excipients, although they are inferior in some aspects to innovator celluloses. Alfacel and Carmacel have the potential to be used as filler, binder, and disintegrant, in the design of tablets. Moreover, one should bear in mind that the differences reported here may be altered because of a possible inter-batch variability and variations in the moisture content.     

New co-processed MCC-based excipient for fast release of low solubility drugs from pellets prepared by extrusion-spheronization

In this study, a new co-processed excipient composed of microcrystalline cellulose (MCC), sorbitol, chitosan and Eudragit® E, easily obtained by wet massing, to increase the dissolution rate of active ingredients of low water solubility from pellets prepared by extrusion–spheronization is evaluated. Indomethacin, nifedipine, furosemide, ibuprofen, prednisolone and hydrochlorothiazide are used as model drugs of different solubility. All pellet formulations evaluated showed adequate morphological, flow and mechanical properties. Pellets prepared with the co-processed excipient show a higher drug dissolution rate than those prepared with MCC and even higher than the pure drug powder. The fast drug dissolution and the complete disintegration (<3?min) of the pellets can be explained by the great porosity of the formulations, the high solubility of the sorbitol, the disintegrant capacity of the chitosan and the distribution of the Eudragit® E polymer particles in-between the other components of the co-processed mixture. In conclusion, this new co-processed excipient is very suitable to increase the dissolution rate of poorly soluble drugs from pellets prepared by extrusion–spheronization. Moreover, the drug release rate can be estimated from the Ln of the drug solubility in acidic medium.     

Evaluation about wettability,water absorption or swelling of excipients through various methods and the correlation between these parameters and tablet disintegration

Objective: To evaluate parameters about wettability, water absorption or swelling of excipients in forms of powders or dosage through various methods systematically and explore its correlation with tablet disintegration.

Material and methods: The water penetration and swelling of powders with different proportions of excipients including microcrystalline cellulose (MCC), mannitol, low-substituted hydroxypropyl cellulose (L-HPC), crospolyvinylpyrrolidone (PVPP), carboxymethyl starch sodium (CMS-Na), croscarmellose sodium (CCMC-Na) and magnesium stearate (MgSt) were determined by Washburn capillary rise. Both contact angle of water on the excipient compacts and surface swelling volume were measured by sessile drop technique. Moreover, the test about water absorption and swelling of compacts was fulfilled by a modified method. Eventually, the disintegration of tablets with or without loratadine was performed according to the method described in USP.

Results and discussion: These parameters were successfully identified by the methods above, which proved that excipient wettability or swelling properties varied with the structure of excipients. For example, MgSt could improve the water uptake, while impeded tablet swelling. Furthermore, in the present study it is verified that tablet disintegration was closely related to these parameters, especially wetting rate and initial water absorption rate. The higher wetting rate of water on tablet or initial water absorption rate, the faster swelling it be, resulting in the shorter tablet disintegration time.

Conclusion: The methods utilized in the present study were feasible and effective. The disintegration of tablets did relate to these parameters, especially wetting rate and initial water absorption rate.     

Use of sodium carbonate and sodium polyacrylate for the prevention of vinegar syndrome

To preserve archive films of which the base material is composed of cellulose acetate, we carried out screening tests on various reagents. We selected sodium carbonate and sodium polyacrylate as an acetic acid gas removing agent and a dehumidification agent, respectively. The performance of sodium carbonate per unit mass in the removal of acetic acid gas was superior to those of commercial products. The presence of sodium carbonate suppressed the increase in concentration of acetic acid gas for several months in film preservation containers. The neutralization of sodium carbonate with acetic acid gas was evaluated quantitatively. Sodium polyacrylate controlled relative humidity at around 40%RH in film preservation containers, and it was effective for film preservation. The dehumidifying performance of sodium polyacrylate compared favourably with those of commercial products. Thus, the materials tested in this study are found to be useful to avoid vinegar syndrome in cellulose acetate-based films.     

Effect of formulation composition on the properties of controlled release tablets prepared by roller compaction

This study discusses the effect of formulation composition on the physical characteristics and drug release behavior of controlled-release formulations made by roller compaction. The authors used mixture experimental design to study the effect of formulation components using diclofenac sodium as the model drug substance and varying relative amounts of microcrystalline cellulose (Avicel), hydroxypropyl methylcellulose (HPMC), and glyceryl behenate (Compritol). Dissolution studies revealed very little variability in drug release. The t₇₀ values for the 13 formulations were found to vary between 260 and 550 min. A reduced cubic model was found to best fit the t₇₀ data and gave an adjusted r-square of 0.9406. Each of the linear terms, the interaction terms between Compritol and Avicel and between all three of the tested factors were found to be significant. The longest release times were observed for formulations having higher concentrations of HPMC or Compritol. Tablets with higher concentrations of Avicel showed reduced ability to retard the release of the drug from the tablet matrix. Crushing strength showed systematic dependence on the formulation factors and could be modeled using a reduced quadratic model. The crushing strength values were highest at high concentrations of Avicel, while tablets with a high level of Compritol showed the lowest values. A predicted optimum formulation was derived by a numerical, multiresponse optimization technique. The validity of the model for predicting physical attributes of the product was also verified by experiment. The observed responses from the calculated optimum formulation were in very close agreement with values predicted by the model. The utility of a mixture experimental design for selecting formulation components of a roller compacted product was demonstrated. These simple statistical tools can allow a formulator to rationally select levels of various components in a formulation, improve the quality of products, and develop more robust processes.     

Effect of Formulation Composition on the Properties of Controlled Release Tablets Prepared by Roller Compaction

This study discusses the effect of formulation composition on the physical characteristics and drug release behavior of controlled‐release formulations made by roller compaction. The authors used mixture experimental design to study the effect of formulation components using diclofenac sodium as the model drug substance and varying relative amounts of microcrystalline cellulose (Avicel), hydroxypropyl methylcellulose (HPMC), and glyceryl behenate (Compritol). Dissolution studies revealed very little variability in drug release. The t₇₀ values for the 13 formulations were found to vary between 260 and 550 min. A reduced cubic model was found to best fit the t₇₀ data and gave an adjusted r‐square of 0.9406. Each of the linear terms, the interaction terms between Compritol and Avicel and between all three of the tested factors were found to be significant. The longest release times were observed for formulations having higher concentrations of HPMC or Compritol. Tablets with higher concentrations of Avicel showed reduced ability to retard the release of the drug from the tablet matrix. Crushing strength showed systematic dependence on the formulation factors and could be modeled using a reduced quadratic model. The crushing strength values were highest at high concentrations of Avicel, while tablets with a high level of Compritol showed the lowest values. A predicted optimum formulation was derived by a numerical, multiresponse optimization technique. The validity of the model for predicting physical attributes of the product was also verified by experiment. The observed responses from the calculated optimum formulation were in very close agreement with values predicted by the model. The utility of a mixture experimental design for selecting formulation components of a roller compacted product was demonstrated. These simple statistical tools can allow a formulator to rationally select levels of various components in a formulation, improve the quality of products, and develop more robust processes.     

静电自组装PDDA/CMCNa聚电解质复合纳滤膜及其性

以聚丙烯腈(PAN)超滤膜为基膜,通过羧甲基纤维素钠(CMCNa)阴离子聚电解质和聚二甲基二烯丙基氯化铵(PDDA)阳离子聚电解质层层静电自组装(LbL)制备得到复合纳滤膜.考察了阴离子聚电解质溶液浓度、组装层数对膜表面荷电性、形貌和亲水性等的影响;同时研究了操作条件不同时该纳滤膜对罗丹明B染料分离性能变化.结果表明,CMCNa阴离子聚电解质浓度增大时,膜表面荷负电性和亲水性增强;当PDDA质量浓度为5.0 g/L,CMCNa的浓度为2.0 g/L,且组装4.0个派对层时,复合膜表面ζ电位约为 70 mV,其接触角约为30°;制备的(5 PDDA/2CMCNa)5.0-PAN复合纳滤膜,在25℃和0.60 MPa的操作条件下,对0.4×10-3 g/L的罗丹明B截留率达到90％,通量为42 L/(m2·h·MPa).     

蒙脱土对纤维素基吸湿衬垫结构与性能的影响

目的在羧甲基纤维素钠(CMC-Na)与壳聚糖(CS)基材中添加纳米蒙脱土(MMT),制备安全无毒、具有良好吸水性的海绵衬垫,可用于鲜肉的保鲜包装。方法将不同比例的MMT添加到CMC-Na和CS混合溶液中,冻干后采用氯化钙交联得到海绵衬垫,测定衬垫在水中的溶胀率和可溶物含量以优化配比,然后测定最优衬垫的吸湿速率、红外光谱、形貌、压缩强度以及色差等。结果当MMT质量分数为5%时,衬垫在水中的溶胀率最高,可溶物含量较低,且与空白对照品相比,由于MMT在高分子基材表面形成大量微米级团聚粒子,所以其比表面积增大,吸湿速率加快。同时,由于MMT良好的力学强度,且与CMC-Na和CS基材结合良好,因此MMT的添加大大提高了衬垫的压缩强度。加入MMT后,虽衬垫的颜色有所加深,但肉眼观察并不明显。结论 MMT的加入可改善CMC-Na/CS衬垫的性能,促进其在鲜肉包装中的实际应用。     

Synthesis and luminescence properties of YVO4:Eu cobblestone - like microcrystalline phosphors obtained from the mixed solvent - thermal method

The mixed solvent-thermal method has been developed for the synthesis of YVO₄:Eu³⁺ luminescent materials in the N, N-dimethylformamide (DMF)/ de-ionized water (DIW) solution. The samples have been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electronic microscope (TEM), UV/vis absorption and photoluminescence spectroscopies. The results demonstrate that we have obtained the uniform YVO₄:Eu³⁺ cobblestone - like microcrystalline phosphors in the mixed solution of DMF and DIW, which are different to the as-obtained YVO₄:Eu³⁺ nanoparticles in pure DIW. And the as - prepared YVO₄:Eu³⁺ microcrystalline particles are composed of numerous nanoparticles. The assembling phenomenon of the nanoparticles is strongly affected by the pH value of the solution and the volume ratio of DMF/DIW. Under UV excitation, the samples can emit the bright red light. While, the photoluminescence (PL) intensities of YVO₄:Eu³⁺ show some difference for samples obtained under the different reaction conditions. This is because that different microstructures of samples result in different combinative abilities between the surface and the adsorbed species so as to produce the different quenching abilities to the emission from Eu³⁺ ions.     

气体膜分离技术在低压瓦斯回收中的应用

说明了有机蒸气膜分离的原理、性能、应用．介绍了大庆炼化公司应用有机蒸气膜分离技术回收低压瓦斯中的C3、C4．原料气进行净化后通过膜装置对瓦斯中的C3以上组分富集，然后通过压缩机把渗透气送到ARGG装置回炼，投用后取得了较大经济效益．     

液相化学还原法制备纳米银及抗菌性能研究

选用液相化学还原法,分别在以羧甲基纤维素钠(Carboxymethyl cellulose sodium,CMC)和葡萄糖为还原剂的体系下制备纳米银颗粒,并进行了对比分析。通过紫外分光光度计、X射线衍射和透射电镜等测试手段对其进行了表征。结果表明,用CMC体系制备的纳米银粉末平均粒径为20～30nm,为多晶结构;用葡萄糖体系制备的纳米银粉末平均粒径为25～35nm,为面心结构。利用抑菌圈法对纳米银的抗菌性能进行测试,结果显示2种体系下制备的纳米银对海洋芽孢杆菌都有很好的抑制作用。     

Preparation of chitosan–sodium alginate microcapsules containing ZnS nanoparticles and its effect on the drug release

Chitosan–sodium alginate microcapsules were prepared in the presence of ZnS nanoparticles via the W/O/W emulsification solvent-evaporation method. Microscopy showed that the microsphere was about 150 nm and by the absorption spectra, ZnS nanoparticles incorporated was 4 nm. Aspirin was chosen to investigate the effect of microcapsules on the drug release. It reveals that comparing with the microsphere without nanoparticles, the release speed of microsphere containing ZnS nanoparticles is significantly decreased from complete release at 10 h to 50% release by 50 h. The data of release kinetics for the microcapsules can be well fitted by the classic Higuchi model.     

用原子力显微镜研究纤维素膜表面形貌和孔径大小及分布

介绍了原子力显微镜 (AFM )的测试原理和用于纤维素膜测定的方法 ,测定了几种纤维素膜的表面形貌 .结果表明 :AFM非常适合用于研究纤维素膜表面形貌结构 ;通过分析纤维素膜表面孔径大小和分布 ,可以较好地解释纤维素膜性能的变化