Amount Of Bridging Liquid Research Articles

Processability and Oral Bioavailability Improvement of Itraconazole by Particle Engineering Technique.

The current study aimed to improve the processability and oral bioavailability of itraconazole (ITZ) via spherical agglomeration. ITZ-spherical agglomerates (ITZ-SA) and ITZ-poloxamer 407-spherical agglomerates (ITZ-PLX-SA) were optimized using Box-Behnken design. Here, the drug release was affected by polymer concentration and stirring speed, whereas particle size was altered by stirring speed, polymer concentration, and amount of bridging liquid. Heckel and Kawakita studies showed a reduction in mean yield pressure and remarkably lowered 1/b value than ITZ, indicating better compactibility and flowability of ITZ-PLX-SA. Physicochemical interactions were not observed during the process, as indicated by ATR-FTIR, DSC, and XRPD. The significant improvement in % drug release of ITZ-PLX-SA was attributed to better wettability and the presence of polymer than ITZ-SA and ITZ. The pharmacokinetic study in rats indicated fivefold enhanced Cmax and twofold improved AUC for ITZ-PLX-SA than plain drug. Thus, spherical agglomeration could improve overall processability and pharmacokinetic profile of ITZ.

Improved micromeritics, packing properties and compressibility of high dose drug, Cycloserine, by spherical crystallization

Cycloserine, a high dose anti-tuberculosis agent, possesses poor flow properties and compression behaviour. The present study was aimed at improving the flowability, packing properties and compressibility of Cycloserine by spherical crystallization. Cycloserine was dissolved in a water and crystallised by pouring into anti-solvent, 1-Butanol, in presence of ethyl acetate which acts as a bridging liquid for formation of agglomeration. Further, spherical agglomeration process for Cycloserine was statistically optimized using the central composite design, keeping the ‘rate of stirring’ and ‘amount of bridging liquid’ as an independent factors and average particle size as the response. Optimized batch of Cycloserine spherical agglomerates (Cyc-SA) was further evaluated for sieve analysis, solid state characterization studies and compaction behaviour (Kawakita analysis and Heckel study). The uniform spherical agglomerates were revealed in microphotographs of scanning electron microscopy while no chemical alteration in the Cycloserine was indicated by X-Ray powder diffraction, differential scanning calorimetry and Fourier-transform infrared spectroscopy during the crystallization. The excellent flow properties of Cyc-SA were demonstrated by Carr's index, Hausner ratio and Kawakita parameters as compare to plain drug. The enhanced particle size and uniform distribution of agglomerates have also contributed to improve flow properties of Cycloserine. Similarly, Heckel parameters like mean yield pressure and yield strength displayed superior compressibility of Cyc-SA. Thus, spherical crystallization would be interesting technique for improving processability of high dose drug like Cycloserine.

Preparation and In Vitro Evaluation of Ibuprofen Spherical Agglomerates.

Ibuprofen, an anti-inflammatory drug, is characterized by poor water solubility, which limits its pharmacologic effects. The present work aimed to the study the effect of agglomeration on the micromeritic properties and dissolution of ibuprofen. Ibuprofen agglomerates were prepared by solvent change method using water, dichloromethane and DMSO as poor solvent, bridging liquid and good solvent respectively in the ratio of 57.5:12.5:30. Process variables such as amount of bridging liquid, mode of addition, temperature and stirring rate were optimized. SEM studies indicate that agglomerates produced were spherical and exhibit irregular shape. X-Ray Powder Diffraction spectra revealed the absence of polymorphism. DSC spectra showed no change in melting point indicating absence of crystal modification. The agglomerates exhibited improved solubility, dissolution rate and micromeritic properties compared to pure drug. Anti-inflammatory studies were conducted in Wistar strain male albino rats and ibuprofen agglomerates showed more significant activity than the pure drug which may be due to better absorption. Ulcerogenic potential study was carried out for pure ibuprofen and agglomerates. Better ulcerogenic potential was observed in ibuprofen agglomerates treated rats.

결정화/응집 기법에 의한 구형 에너지 복합체 제조 및 그 열분해 특성

Spherical DADNE/AP (1,1-diamino-2,2-dinitroethylen/ammonium perchlorate) energetic composites were produced by drown- ing-out/agglomeration (D/A). The agglomeration of DADNE with AP particles was found to be affected by the amount of the bridging liquid, stirring velocity and residence time. The composites appeared to grow dramatically with the amount of bridging liquid which triggers agglomeration. As the stirring velocity and the residence time increased, the size of composites increased and then tended to decrease. Thermal gravimetric analysis showed that the addition of DADNE activates the low temperature decomposition (LTD) of AP. For the neat AP, the only about 30 wt% of AP was found to decompose at the LTD. On the other hand, it was found that 70 wt% of AP decomposed when DADNE was added by physical mixing and 90 wt% of AP decomposed when the DADNE/AP composites were prepared by the D/A method.

Preparation and, in vitro, preclinical and clinical studies of aceclofenac spherical agglomerates

Aceclofenac agglomerates were prepared by spherical crystallization technique using a three solvent system comprising acetone: dichloromethane (DCM): water (bridging liquid, good solvent and bad solvent, respectively). Hydroxypropyl methylcellulose-50 cps (HPMC) in different concentrations was used as hydrophilic polymer. The effect of speed of rotation and amount of bridging liquid on spherical agglomeration were studied. The agglomerates were subjected to various physicochemical evaluations such as practical yield, drug content, particle size, loss on drying, porosity, IR spectroscopy, differential scanning calorimetry, X-ray diffraction studies, relative crystallinity, scanning electron microscopy, micromeritic properties, solubility and dissolution studies. The agglomerates showed improved micromeritic properties as well as dissolution behaviour in comparison to conventional drug crystals. The optimized agglomerates (F-9) showed good sphericity as well as high drug release, and hence they were compressed into tablets by direct compression. The tablets were found within the limits with respect to various physicochemical parameters. The dissolution rate of prepared tablets was better than that of marketed tablet and pure drug. The optimized agglomerates and tablet formulations were found to be stable for 6 months under accelerated conditions. The in vivo studies (preclinical pharmacokinetics, pharmacodynamics and toxicity studies, and clinical pharmacokinetics) of optimized agglomerates were carried out. The results of preclinical studies revealed that the agglomerates provided improved pharmacodynamic and pharmacokinetic profiles of drug besides being nontoxic. The results of pharmacokinetic studies of optimized tablet in human subjects indicated improved pharmacokinetic parameters of drug in comparison with that of marketed tablet.

Preparation of sustained-release nitrendipine microspheres with Eudragit RS and Aerosil using quasi-emulsion solvent diffusion method

Sustained-release nitrendipine microspheres were prepared in liquid system by quasi-emulsion solvent diffusion method, in which the Aerosil was employed as an inert dispersing carrier to improve the dissolution rate of nitrendipine, and Eudragit RS as a retarding agent to control the release rate. The resultant microspheres were evaluated for the recovery, bulk density, average particle size, drug loading, and incorporation efficiency. And the factors affecting the formation of microspheres and the drug-release rate were investigated. It was observed by a scanning electron microscope (SEM) that the microspheres were finely spherical and uniform, and no entire nitrendipine crystals were observed visually. The results of X-ray diffraction indicated that nitrendipine in microspheres was disordered, suggesting that nitrendipine was highly dispersed in microspheres. The drug loading of microspheres was enhanced with increasing the ratio of drug to excipients, and the incorporation efficiency was always >90%. The formation of microspheres was mainly influenced by the amount of bridging liquid and sodium dodecyl sulfate (SDS) in poor solvent. The dissolution profiles could be modulated with adjusting the amount of retarding agent and dispersing carrier formulated.

Preparation and characteristics of microcapsules containing enoxacin by one continuous process of agglomeration and microencapsulation.

A novel microencapsulation technique was carried out with the phase separation of Eudragit RS from the wet spherical agglomeration (WSA) system by non-solvent addition. To elucidate the characteristics of microcapsules the spherical agglomerates containing enoxacin (ENX), lactose or Avicel which are different in their affinity to water (i.e. insoluble, soluble or absorbable properties, respectively), were prepared as core particles in an acetone/n-hexane mixture (volume ratio 3/7) by a WSA technique. The size of all kinds of spherical agglomerates was controlled by the amount of bridging liquid (ammonia water or distilled water) used. In the microencapsulation process encapsulation was performed efficiently at 400-600 rpm. Avicel agglomerates could be coated up to 30 per cent with Eudragit RS with less aggregation. Various additives were compared as additions into the system to avoid the aggregation of encapsulated particles. Addition of more than 3 per cent magnesium stearate based on the core weight in the system, before or at the same time as phase separation of Eudragit RS occurred, resulted in low aggregation of microcapsules for spherical agglomerates containing ENX or lactose. In formulating a water-absorbable excipient such as Avicel in the agglomerates of ENX, adding some 10 per cent Eudragit RS-dichloromethane solution into the WSA system, and using magnesium stearate as a protective agent, the resultant microcapsules could be obtained efficiently without aggregation, showing sustained release of ENX depending on coating level.

The Role of Compaction in Agglomeration in Liquid and Formulation of Scale-up Equation.

The effects of agitation intensity and amount of bridging liquid on agglomerate formation in agglomeration in liquid were experimentally investigated. An increase in agitation intensity advanced the compaction of agglomerates, reduced the porosity and changed the saturation degree which is the ratio by volume of the bridging liquid to the pores of an agglomerate. It was observed that the process of agglomerate growth depended on the changes in porosity. Based on this observation, the effects of agitation intensity on the process of compaction and changes in porosity were quantitatively elucidated and a scale-up equation was formulated. In addition, model agglomerates of the zirconia powder were cold isostatically pressed to investigate the influence of green agglomerate porosity on the density of sintered agglomerates. The results showed that the agglomerates produced by agglomeration in liquid must have porosities less than 0.51 in order to achieve high density and strength after sintering. To achieve this objective, the formulated scale-up equation was utilized to design a batch-type horizontal agglomerator that can provide the agitation energy required to produce agglomerates with porosities below 0.51. The newly designed agglomerator was successfully tested in the production of highly dense microspherical agglomerates of zirconia.

Beneficiation of Char, from a Pyrolyzed Eastern Canadian Coal, by Aggregative Flotation†

A high-volatile high-sulphur coal was pyrolysed at pressures of 50 and 500torr, and at temperatures from 390 to 660°C. The floatability of the chars and the removal of ash and mineral sulphur from the char by aggregative notation were studied using a high-shear blender and a laboratory-scale flotation column. With respect to efficiency of cleaning, low temperature chars were better than high, and high pressure chars better than low. The inherent pH of char-water slurries increased from 4 to 10 as the temperature of pyrolysis was raised from 390 to 660°C. The amount of bridging liquid required to achieve 90% recovery of product, and the calculated floatability coefficient, were found to be functions of the specific surface area of the char.

The physicochemical parameters determining the size of agglomerate prepared by the wet spherical agglomeration technique

Lactose samples of five different particle sizes from 31 to 261 μm dispersed in chloroform were agglomerated with a small amount of saturated aqueous lactose solution which acted as a bridging liquid to wet the particles preferentially. The effects of raw particle size and the amount of bridging liquid on the average size of resultant agglomerate were investigated. The agglomerate size increased with decreasing size of lactose. This effect was enhanced by increasing the amount of bridging liquid for lactose less than 79 μm. A linear correlation on a log—log plot was observed between the agglomerate size and the saturation ratio of bridging liquid. The slope increased with decreasing particle size of lactose. The size distribution of agglomerates was also determined for the particle size of lactose and the amount of bridging liquid used. The physicochemical properties of the bridging liquid, i.e. contact angle and interfacial tension, were also taken into account for interpreting the agglomerate size. The correlation between the agglomerate size and the above parameters was represented quantitatively by eqn. (10) in the text. The parameter n, which varies directly with agglomerate size, increased with increasing saturation ratio, or with decreasing lactose particle size.

Spherical Agglomeration of Naproxan by Solvent Change Method

Naproxen, an anti-inflammatory drug, exhibits poor water solubility and flow properties. Spherical agglomerates were prepared by solvent change method. Solvent composition for spherical agglomeration was determined by constructing ternary diagram. Crystallization medium used for spherical agglomerates of naproxen consisted of tetra-hydro-furan (good solvent); water (poor solvent); isopropyl acetate (bridging liquid) in the ratio of 29:61:10, respectively. Spherical agglomerates were characterized by differential scanning calorimetry, infrared spectroscopy, X-ray diffractometry and scanning electron microscopy. Micromeritic and dissolution behavior studies were carried out. Process variables such as amount of bridging liquid, stirring time and duration of stirring were optimized. Dissolution profile of the spherical agglomerates was compared with pure sample and recrystallized sample. Spherical agglomerates exhibited decreased crystallinity and improved micromeritic properties. The dissolution of the spherical agglomerates was not improved compared with pure sample because the dissolution of naproxen dependent on particle size or surface area. Key words: Spherical agglomerates; Naproxen; Crystallinity; Dissolution.DOI: http://dx.doi.org/10.3329/sjps.v4i1.8860 SJPS 2011; 4(1): 1-8