Directly Compressible Acetaminophen Compositions Prepared by Fluidized-Bed Granulation

Abstract

Polyvinylpyrrolidone (PVP) in aqueous solution was used as a binding agent in a fluidized-bed system to agglomerate acetaminophen powder into directly compressible granules. It was found that a minimal amount of 5% w/w PVP in a concentration of 7.5% w/v or less was needed to produce granules with an acceptable flow and the corresponding tablets having enough hardness without capping. There was a strong correlation between the time for 80% dissolved (T₈₀) and the logarithm of granule volume-surface mean diameter. A directly compressible acetaminophen composition to manufacture tablets having a T₈₀ value less than 30 min can be prepared simply by adding an appropriate amount of disintegrant (crospovidone, sodium starch glycolate, or pregelatinized starch) to the agglomerated granules.     

Fluidized-Bed agglomeration of acetaminophen; direct compression of tablets and physiologic availability

A novel process was developed for manufacturing acetaminophen in a free-flowing, directly compressible agglomerated form, involving spray agglomeration of acetaminophen powder with polyvinylpyrrolidone (PVP) in isopropyl alcohol as a bonding agent using a fluidized-bed granulator. Agglomerates prepared with 5% PVP yielded a free-flowing and compressible material. Upon lubrication with 0.5% magnesium stearate, the material was found to be directly compressible into tablets. To improve dissolution and tableting properties, the agglomerates were compressed into tablets after blending with varying weight ratios of microcrystalline cellulose/pregelatinized starch as a filler/disintegrant combination. The final stable tablet formulation consisted of agglomerates equivalent to 325 mg of acetaminophen, 2.1 mg of magnesium stearate, and the filler/disintegrant in a weight ratio of 70:30 to yield a tablet weight of 425 mg. Physical properties and dissolution profile of these tablets were comparable to those of a commercial acetaminophen tablet. Physiologic availability calculated using the urinary excretion method indicated half-lives of 2.0, 2.1, and 2.2 hours for control (acetaminophen powder), experimental tablet, and a marketed product, respectively.     

Increasing the aqueous solubility of acetaminophen in the presence of polyvinylpyrrolidone and investigation of the mechanisms involved

It was shown that the aqueous solubility of acetaminophen in the presence of polyvinylpyrrolidone (PVP) increased. The solubility at 25°C increased from 14.3 mg mL^-1 in the absence of PVP, to 19.7 mg mL^-1 in the presence of 4% w/v PVP, and to 26.7 mg mL^-1 in the presence of 8% w/v PVP. Dialysis studies indicated that there is a potential of binding between PVP and acetaminophen in their aqueous solutions. Dialysis studies also revealed that the nature of interaction between PVP and acetaminophen is physical and reversible, and there was no strong binding between PVP and acetaminophen in their solutions. Infrared spectroscopy of acetaminophen/PVP solid dispersion indicated that the mechanism of interaction between PVP and acetaminophen is via hydrogen bonding. Therefore, the increase in solubility of acetaminophen in the presence of PVP is probably attributed to its ability to form a water-soluble complex with PVP.     

Mechanisms of Drug Release from Matrices Prepared with Aqueous Dispersion of Ethylcellulose

The objective of this study was to investigate the mechanism of acetaminophen (APAP) release from tablets prepared by the wet granulation method using an aqueous polymeric dispersion (Surelease) as a granulating agent. Tablets compressed from granules containing 10% w/w acetaminophen and 13.44% w/w total solids from Surelease released only 52.4% w/w drug after 120 min of dissolution testing, while controlled tablets without Surelease released 94.1% w/w drug. In order to prepare control tablets of 6.8 Kp hardness value, the upper compressional force recorded was 15.87 kN while tablets containing 13.44% w/w of total solids from Surelease had a recorded force of 6.28 kN. The drug release from tablets prepared with Surelease as a granulating liquid followed the diffusion-controlled model for an inert porous matrix     

Effects of Temperature,Humidity, and Aging on the Disintegration and Dissolution of Acetaminophen Tablets

Abstract

The effect of storage for 8 weeks at 40°C in moderate and high humidity on acetaminophen tablets prepared by the wet granulation method using povidone or pregelatinized starch as a binder was studies. Storage at 52% relative humidity produced an increase in hardness of acetaminophen tablets and storage at 94% relative humidity caused a decrease in hardness. In all cases tablets granulated with pregelatinized starch were less susceptible to change caused by humidity than tablets granulated with povidone. The disintegration of tablets containing starch or povidone was slowed as the humidity was increased. Tablets stored at 40 =C and 94 V. relative humidity showed a substantial slowing of dissolution, but there was little change of dissolution of tablets when aged at 40 -C / 52% relative humidity. In comparing starch and povidone as binders, acetaminophen tablets prepared with pregelatinized starch were less effected by high humidity than tablets prepared with povidone.     

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.     

Application of moisture activated dry granulation (MADG) process to develop high dose immediate release (IR) formulations

Moisture activated dry granulation (MADG) method was used to develop IR tablets with cohesive, fluffy and high dose drugs. To evaluate this approach, three drugs: metformin hydrochloride, acetaminophen and ferrous ascorbate were selected as model compound along with three binders: maltodextrin DE16, PVP K 12 and HPC. The granules were generated using MADG method and tablets were prepared using rotary tablet press. The granules and tablets were characterized for particle size analysis, flow properties, tablet hardness, friability, moisture content, dissolution study, disintegration time and stability study. All results were found to be within acceptable limits. Development of all formulation tablets were found as best fitted for an immediate release of Metformin hydrochloride, acetaminophen and ferrous ascorbate. MADG delivered a robust manufacturing process for generation of granules with excellent flowability. The tablets prepared using this method were found to show better content uniformity, good compactability and low friability. Use of this approach aids to lower the amount of excipients used to overcome physiochemical limitation of the drug substances and there side effects. Both drying and milling steps in wet granulation were not required for MADG process. MADG became a cost effective process which could lead to reduced total tablet size and also save time.     

Tablet Properties and Dissolution Characteristics of Compressed Cellulose Acetate Butyrate Microcapsules Containing Succinyl Sulfathiazole

Cellulose acetate butyrate microcapsules of succinyl sulfathiazole were prepared by a modified emulsion-solvent evaporation method and formulated for compression with microcrystalline cellulose and carboxymethyl starch. Tablet hardness decreased and friability increased as microcapsule content increased. Formulations containing up to 50% microcapsules produced satisfactory tablets, but at 70% microcapsules, the tablets were unacceptably fragile. Variation of microcapsule size fraction from 75 μm up to 428 μm had only a small effect on tablet properties when formulated at the 40% level. Tablet hardness increased with increasing compression pressure from 1.9 kg at 17.6 MPa to 14.9 kg at 210.7 MPa. Dissolution properties of the microcapsules were essentially unchanged at compression pressures up to 351 MPa with T_50% values ranging from 121 to 132 minutes. Uncompressed microcapsules had a T_50% value of 130 minutes.     

Influence of granulating method on physical and mechanical properties, compression behavior, and compactibility of lactose and microcrystalline cellulose granules

The physical and mechanical properties of lactose (LC) and microcrystalline cellulose (MCC) granules prepared by various granulating methods were determined, and their effects on the compression and strength of the tablets were examined. From the force-displacement curve obtained in a crushing test on a single granule, all LC granules appeared brittle, and MCC granules were somewhat plastically deformable. Intergranular porosity ε_inter clearly decreased with greater spherical granule shape for both materials. Decrease in intragranular porosity ε_intra enhanced the crushing force of a single granule F_g. Agitating granulation brought about the most compactness and hardness of granules. In granule compression tests, the initial slope of Heckel plots K₁ appeared closely related to ease of filling voids in a granule bed by the slippage or rolling of granules. The reciprocal of the slope in the succeeding step 1/K₂ in compression of MCC granules indicated positive correlation to F_g, while in LC granules, no such obvious relation was evident. 1/K₂ differed only slightly among granulating methods. Tensile strength of tablets T_t obtained by compression of various LC granules was low as a whole and was little influenced by granulating method. For MCC granules, which are plastically deformable, tablet strength greatly depended on granulation. Granules prepared by extruding or dry granulation gave strong tablets. Tablets prepared from granules made by the agitating method showed particularly low T_t. From stereomicroscopic observation, the contact area between granule particles in a tablet appeared smaller; this would explain the decrease in intergranular bond formation.     

Release Kinetics and Availability of Mebeverine Hydrochloride from Polycarbophil Loaded by Swelling

The release rate and mechanism of release of mebeverine hydrochloride were studied for commercial “Duspatalin” tablets and for different tablet formulations (F₁, F₂ & F₃) containing 20, 40 and 65% polycarbophil, respectively. The formulated granules were obtained by freeze drying of polycarbophil granules loaded with aqueous solution of the drug at 25°C by swelling of the polymer. The release of mebeverine hydrochloride from prepared tablet formulations was faster than that of Duspatalin tablets. The release rate of the drug increased as the polycarbophil content of the tablets increased. The calculated correlation coefficients for the release data fitted to various models showed that the release from Duspatalin tablets and F₂ follow first order kinetics, while release of F₁ approaches that of zero order. The release mechanism from F₃ could not be determined. DSC thermograms showed that there is an interaction between the drug and the polymer in aqueous medium, but not in the solid state.

The in-vivo guinea-pig studies revealed that mebeverine hydrochloride was released and absorbed from the tested formula (F₃), depressed the agonists-induced contractions 2 hrs after treatment but not after 4 hrs indicating rapid absorption and metabolism. The percentage inhibitions ranged from 40-85%. The treatment seems to antagonise barium chloride (BaCl₂)-induced contractions more than those induced by carbochol.     

Effects of hydrophilic excipients and compression pressure on physical properties and release behavior of aspirin-tableted microcapsules.

Aspirin ethylcellulose microcapsules were tableted by compression with or without excipients (lactose or polyvinylpyrrolidone [PVP]). The effects of the amount of the excipients and microcapsule size on the crushing strength and release rate of aspirin from tableted microcapsules were investigated. Tablets without excipients had a crushing strength that was independent of the applied pressure and microcapsule size. An increase in compression pressure from 15 to 60 MPa resulted in an increase in the crushing strength of tablets containing 20% or 40% w/w lactose, but the reverse results were obtained for the tableted microcapsules containing 20% or 40% w/w PVP. Results showed that the release rate of aspirin from microcapsules containing lactose or PVP was independent of the compression pressure with the exception of tablets containing 40% w/w lactose. In vitro release profiles of aspirin from tableted microcapsules containing lactose or PVP showed that increasing the concentration of the excipients resulted in an increase in the release rate of aspirin. Values of n were changed by the compression pressure and the added excipients.     

Effects of Hydrophilic Excipients and Compression Pressure on Physical Properties and Release Behavior of Aspirin-Tableted Microcapsules

Aspirin ethylcellulose microcapsules were tableted by compression with or without excipients (lactose or polyvinylpyrrolidone [PVP]). The effects of the amount of the excipients and microcapsule size on the crushing strength and release rate of aspirin from tableted microcapsules were investigated. Tablets without excipients had a crushing strength that was independent of the applied pressure and microcapsule size. An increase in compression pressure from 15 to 60 MPa resulted in an increase in the crushing strength of tablets containing 20% or 40% w/w lactose, but the reverse results were obtained for the tableted microcapsules containing 20% or 40% w/w PVP. Results showed that the release rate of aspirin from microcapsules containing lactose or PVP was independent of the compression pressure with the exception of tablets containing 40% w/w lactose. In vitro release profiles of aspirin from tableted microcapsules containing lactose or PVP showed that increasing the concentration of the excipients resulted in an increase in the release rate of aspirin. Values of n were changed by the compression pressure and the added excipients.     

基于核磁共振和超声波探伤技术的混凝土耐久性分析

针对核磁共振试验过程中试件尺寸受限问题,采用超声波探伤技术对混凝土内部孔隙率的变化进行表征.采用冻融循环试验加速混凝土的退化,结合超声波探伤技术测得的超声波波速和核磁共振技术测得的T2谱对试件内部孔隙率的变化进行表征.研究结果表明:混凝土在冻融循环退化过程中,T2谱中有三个波峰,其中表示试件内部微细小裂缝的主峰面积占总...     

Formulation Optimization of Diltiazem Hydrochloride Matrix Tablets Containing Modified Ispaghula Husk Using Factorial Design

The purpose of this study was to develop modified-release tablets of diltiazem hydrochloride using physically modified ispaghula husk as a hydrophilic matrixing agent. Ispaghula husk and water were exposed to heat in a hot air oven or microwave oven. The treated samples were evaluated for swelling and rigid gel formation. Microwave oven treated samples showed rigid gel formation and hence they were systematically studied using 3² factorial design using heating time and amount of water as independent variables. Diltiazem tablets were prepared using treated samples and analyzed for in vitro drug release. A polynomial equation was generated using statistically significant terms such as heating time, X₁, amount of water, X₂, and X₁X₂ and X₁² for predicting time required for 80% drug dissolution. Heating time was found to have a predominant effect in sustaining the drug release. A contour plot is presented for interpretation of the results. The tablets exhibited more axial swelling than radial swelling. The results of F-statistics revealed that the drug release pattern fit well in the Higuchi model.     

An algorithm for locating short circuits among N signal paths usingK-port parallel short detector

To locate short circuits on a printed circuit board, a K-port parallel short detector can test K signal paths simultaneously. If the total number of signal paths N on a printed circuit board is larger than K, then we need to divide the testing process into multiple stages such that at most R signal paths are tested in each stage. In this paper, we design a parallel algorithm to locate all the short circuits among the N signal paths on a printed circuit board using a K-port parallel short detector where Ki's such that S_i contains at most K signal paths, and then it bisects S_i into two disjoint sets T_2i-1 and T_2i, (2) it locates all the short circuits in S_i for all i, and (3) it locates all the short circuits between S_i and S_j for all i≠j by testing T_2i-1 against T_2j-1, T_2i-1 against T_2j, T_2i against T_2j-1, and T _2i against T_2j     

Aging and Mechanical Properties of AI-Li/SiCp Composite Produced by Mechanical Milling and Extrusion Processing

In the present study, the effect of aging behavior on the microstructure and mechanical properties of submicron SiC particulate-reinforced Al-Li composites was investigated, including the quenching sensitivity. The results showed that the age-hardening of AI-Li/SiCp composite was accelerated with an increase in the aging temperature and the amount of SiC particulates. Microstructural characterization studies revealed that the microstructurcs of aged Al-Li/ 10vol%SiCp composite consisted of T₁ T₂ phase, S^'phase, δ^' phase. The quenching sensitivity of solution-treated AI-Li/10vol%SiCp composite was low, and was independent of the cooling rate, while the sensitivity of T6-treated samples increased with a decrease in the cooling rate because of precipitation of the T₁ phase and T₂ phase.     

N掺杂C包覆NaTaO3复合材料制备及其可见光催化性能

以五氯化钽(TaCl₅)、乙酸钠为原料,三聚氰胺为N源,十六烷基三甲基溴化铵(CTAB)和聚乙烯吡咯烷酮(PVP)为表面活性剂,通过溶胶-凝胶法制备了N掺杂C包覆NaTaO₃复合材料。采用XRD、TEM、XPS、UV-Vis DRS等对样品进行表征,以罗丹明B(RhB)溶液为目标降解物,测试了不同N比例掺杂的复合材料的吸附性能和光催化性能。结果表明,加入的CTAB和PVP经过N₂保护的热处理后在NaTaO₃周围形成超薄的碳膜,不仅限制NaTaO₃粒径增长,而且提高复合材料对目标污染物的吸附性。N掺杂C包覆NaTaO₃复合材料具备良好的可见光催化活性,其中三聚氰胺与TaCl₅的摩尔比n为1.5时,制备的N掺杂C包覆NaTaO₃复合材料可见光催化效率最高,暗中吸附80 min、可见光照8 h时,RhB的去除率为96.46%,其光催化反应过程符合准一级反应动力学规律。      

WC-40%Al2O3复合粉末二步热压烧结

以高能球磨机械合金化制得的WC-40%Al₂O₃复合粉末为原料,采用二步热压烧结法制备复合块体。首先将粉末坯体在压力条件下加热到较高的温度 T₁,获得相对致密的坯体结构,此时存在临界的可收缩气孔,然后将其保温在一个相对较低的温度 T₂,通过低温保温实现致密化。由于烧结过程温度相对较低,晶粒长大被有效抑制。采用XRD、SEM、扫描探针（SPM）对复合材料的物相、微观结构进行表征,并进行正交实验分析第二步烧结温度以及保温时间对复合块体微观组织和力学性能影响。结果表明：当 T₁=1600 ℃、T₂=1450 ℃保温6 h时,WC-40%Al₂O₃复合材料成形致密度达到99.03%,维氏硬度和断裂韧性分别为18.36 GPa和10.4 MPa·m^1/2,抗弯强度为1162.1 MPa.     

中、小型厅堂声场均匀度研究

声学参量在声场中的分布情况,影响厅堂的音质效果.以一个中型会议室为例,采用Odeon软件,模拟分析了两种声源情况下,材料的布置与形状对中、小型厅堂声场均匀度的影响.结果 表明中、小型厅堂后墙吸声材料的布置对均匀度的影响较小;材料的布置与形状对早期衰减时间(Early Decay Time,EDT)与混响时间T30均匀度...     

Continuous direct tablet compression: effects of impeller rotation rate,total feed rate and drug content on the tablet properties and drug release

Context: Continuous processing is becoming popular in the pharmaceutical industry for its cost and quality advantages.

Objective: This study evaluated the mechanical properties, uniformity of dosage units and drug release from the tablets prepared by continuous direct compression process.

Materials and methods: The tablet formulations consisted of acetaminophen (3–30% (w/w)) pre-blended with 0.25% (w/w) colloidal silicon dioxide, microcrystalline cellulose (69–96% (w/w)) and magnesium stearate (1% (w/w)). The continuous tableting line consisted of three loss-in-weight feeders and a convective continuous mixer and a rotary tablet press. The process continued for 8?min and steady state was reached within 5?min. The effects of acetaminophen content, impeller rotation rate (39–254?rpm) and total feed rate (15 and 20?kg/h) on tablet properties were examined.

Results and discussion: All the tablets complied with the friability requirements of European Pharmacopoeia and rapidly released acetaminophen. However, the relative standard deviation of acetaminophen content (10% (w/w)) increased with an increase in impeller rotation rate at a constant total feed rate (20?kg/h). A compression force of 12?kN tended to result in greater tablet hardness and subsequently a slower initial acetaminophen release from tablets when compared with those made with the compression force of about 8?kN.

Conclusions: In conclusion, tablets could be successfully prepared by a continuous direct compression process and process conditions affected to some extent tablet properties.