Solubility and Dissolution of Etoposide from Solid Dispersions of PEG 8000

The Solubility and dissolution of etoposide from solid dispersion of PEG 8000, prepared by the fusion method, were investigated. Stability studies revealed that the etoposide was stable in water for three days at 37 ± 0.5°C alone and as a physical mixture with PEG 8000. However, nearly 5% decomposition was oberved in aqueous solutions made from solid dispersions. TLC, IR and HPLC studies showed both the drug and carrier were stable during the fusion process. Aqueous solubility of etoposide from solid dispersions with etoposide: PEG 8000 ratios of 1:5, 1:10, 1:20, 1:30 and 1:40, was studied at 37 ± 0.5°C, and found to be significantly higher than that of etoposide alone or from its physical mixtures with PEG 8000. These dispersions increased the solubility of etoposide by 32.3%, 96.8%, 133.5%, 280.7% and 326.6% respectively compared to that of etoposide alone, whereas only 1:40 etoposide: PEG 8000 physical mixture demonstrated a significant increase in etoposide solubility (16.1%). Dissolution studies, on the solid dispersions in water at 37 ± 0.5°C, revealed a marked increase in the dissolution rate of etoposide from 1:20, 1:30 and 1:40 solid dispersions with 100% drug dissolving within 1 minute; dissolution time for 1:5 and 1:10 dispersions, and all physical mixtures was 3 minutes while etoposide alone required 30 minutes for complete drug dissolution. The melting behavior of the etoposide-PEG 8000 mixtures and subsequent thermal analysis of the melts suggested that the increase of solubility of etoposide was mostly due to the formation of a solid solution of etoposide in PEG 8000.     

Development of a New Tablet Formulation of Theophylline: In Vitro and in Vivo Studies

The preparation of a new scored 250 mg theophylline tablet is described, for which effects of particle size of the active principle, aspects of granulation and changes in tabletting settings were investigated.

In vitro studies showed the dissolution rate from tablets prepared from theophylline of commercial quality (50 μm) or of selected particle size (30 μm) to be faster than that from tablets prepared from micronized theophylline (10 μm). In vivo studies in dog showed that only the tablet from theophylline of selected particle size has the same bioavailability as an aqueous solution.

The scale up study showed that the characteristics of the tablets, including dissolution rate, are independent of the formulation factors.     

A novel apparatus for the determination of solubility in pressurized metered dose inhalers

The accurate solubility of salbutamol sulfate, budesonide, and formoterol fumarate dihydrate in hydrofluoroalkane propellant 134a at 25°C for 24 h, are reported. The authors describe a novel reusable in-line pressurized solubility apparatus containing an integral filter holder and a continuous decrimpable valve for the determination of drug/excipients solubility in pressurized metered dose inhalers. The solubility was determined by high-performance liquid chromatography. Solubility of salbutamol sulfate was determined as being below the detection limits while budesonide and formoterol fumarate dihydrate solubility were 23.136 ± 2.951 μg.g^-1 and 0.776 ± 1.023 μg.g^-1, respectively (n = 3). This novel solubility apparatus offers an improved ease of use and potential higher analytical throughput.     

Nimesulide and beta-cyclodextrin inclusion complexes: physicochemical characterization and dissolution rate studies

Complex formation of nimesulide (N) and β-cyclodextrin (βCD) in aqueous solution and in solid state and the possibility of improving the solubility and dissolution rate of nimesulide via complexation with βCD were investigated. Phase solubility studies indicated the formation of a 1:1 complex in solution. The value of the apparent stability constant Kc was 158.98 M^-1. Solid inclusion complexes of N and βCD were prepared by kneading and coevaporation methods. Differential scanning calorimetry (DSC) studies indicated the formation of solid inclusion complexes of N-βCD at a 1:2 molar ratio in both the methods. Solid complexes of N-βD (1:1 and 1:2 M) exhibited higher rates of dissolution and dissolution efficiency values than the corresponding physical mixtures and pure drug. Higher dissolution rates were observed with kneaded complexes than with those prepared by coevaporation. Increases of 25.6- and 38.7-fold in the dissolution rate were observed, respectively, with N-βCD 1:1 and 1:2 kneaded complexes.     

Relationship Between Particle Size and Dissolution Rate of Bulk Powders and Sieving Characterized Fractions of two Qualities of Orthoboric Acid

We have carried out a study of the particle size distribution and aqueous dissolution rate of two commercially available qualities of orthoboric acid, labeled “crystal” (ABC) and “powder” (ABP). In a previous work, we have shown that the two commercial qualities of orthoboric acid chosen as model compound (“powder” and “crystal”) are related to the same crystal network in spite of their dvferent names. However, these two qualities have very different size particle distributions, as previously determined by sieving and confirmed by the present laser light scattering study. Dissolution testing is performed under sink conditions and show that the bulk ABC quality dissolves far more rapidly that the bulk ABP quality, For each quality, dissolution rates of four sieved particle size fractions (0-90 μm; 90-125 μm; 125-180 μm; 180-250 μm) were compared. Concerning the ABC quality, comparisons were also done with three other particles size fractions: 250-355 μm, 355-500 μm, and 500-710 μm. This study used the dQ/dt versus t profile. Dissolution profiles of the fractions enclosing particles with a size superior to 125 μm are very close. On the other hand, fractions enclosing particles with a size smaller than 90 μm present a different profile and a slower rate of dissolution.     

The use of lipid-based formulations to increase the oral bioavailability of Panax notoginseng saponins following a single oral gavage to rats

Purpose: This article was intended to improve the absorption of ginsenoside Rg1 and Rb1 of Panax notoginseng saponins (PNS). Methods: PNS-Phospholipid complex and a lipid-based formulation by dissolving the complex in the medium chain fattyglycerides were prepared, and their oral relative bioavailability was determined in rats and compared with an aqueous solution of PNS for each component. Results: The study gave evidence that the phospholipids could combine with the two active constitutes of PNS and form a PNS-phospholipid complex. The complex efficiently increased the solubility of hydrophilic ginsenoside Rg1 and Rb1 in some selected hydrophobic esters, such as fatty glycerides, and constructed the lipid-based formulations of PNS. The experimental result in rats in vivo showed that the oral relative bioavailability was enhanced remarkably by these lipid-based formulations composed of the PNS-Phospholipid complex and various esters. The absorption enhancement of the medium-chain glyceride (Labrafac cc and Capmul MCM (3:1)) was somewhat greater than that of other fatty glyceride. The area under the plasma concentration-time curve (AUC) of ginsenoside Rg1 and Rb1 of the PNS-complex in the medium-chain glyceride were 27.38 μg.mL-1.h and 600.08 μg.mL-1.h, compared with 2.52 μg.mL-1.h and 92.29 μg.mL-1.h of the PNS aqueous solution, respectively. Conclusions: The oral relative bioavailability of ginsenoside Rg1 and Rb1 of PNS was enhanced remarkably by the lipid-based formulations. These findings reveal a new strategy to increase oral bioavailability by lipophilicity enhancement for some highly water-soluble but poorly absorbed drugs.     

The influence of diluent on the release of theophylline from hydrophilic matrix tablets

The role of β-cyclodextrin (β-CD) on the apparent solubility of theophylline was investigated by the solubility method. Binary systems of theophylline and β-CD were prepared using the dry co-grinding method. Their characterization was performed by differential scanning calorimetry (DSC). The dissolution rate of theophylline and theophylline/β-CD and dissolution studies of matrix tablets prepared from mixtures containing theophylline and ground theophylline were carried out. It can be concluded that β-CD is related to an increase in the apparent solubility and dissolution rate of the drug, promoting improvement on the release of theophylline from matrices manufactured with hydroxypropylmethylcellulose (HPMC). This can be attributed to the amorphous state and the increased wettability of the drug.     

A Comparison of the Properties of Some Chloramphenicol and Neomycin Eye Ointments, Commercially Available in the U.K

The rheology, particle size distribution and drug release, measured by dissolution and agar diffusion techniques, of five B.P. Chloramphenicol Eye Ointments and three B.P. Neomycin Eye Ointments have been examined. All ointments showed structural breakdown during continuous shear rheology. Three chloramphenicol ointments displayed spur values whilst one neomycin ointment displayed a bulge on the up-curve of the rheogram. Mass median particle sizes ranged from 6.0 to 13.0 and 5.4 to 9.6 μm for the chloramphenicol and neomycin ointments respectively. Drug release similarly varied. By dissolution techniques the quantity of chloramphenicol that dissolved in 60 minutes ranged from 22 to 41 μg whilst agar diffusion studies produced drug releases which varied from 2.4 to 4.7 and 0.8 to 2.3 μg for the chloramphenicol and neomycin results respectively.     

Inclusion Complexation of Lorazepam with β — Cyclodextrin

The preparation of an inclusion complex of Lorazepam, a benzodiazepine antianxiety agent with β -cyclodextrin is described. The inclusion compound was prepared by the homogeneous coprecipitation method in the molar ratio of 1:2 of the drug and β -cyclodextrin respectively. The formation of inclusion complex was evaluated by UV spectral studies, IR studies, X-ray diffractometry, and Differential Thermal Analysis. The solubility and in-vitro drug release studies indicated that the complex form of the drug significantly increase the solubility and the dissolution rate compared to the free form. Tablets prepared with Lorazepam- β -cyclodextrin complex also showed a significant increase in dissolution of the drug indicating that P-cyclodextrin plays an important role in the solubilization of the drug.     

Inclusion complexation of nimesulide with beta-cyclodextrins

Nimesulide (NM), a nonsteroidal anti-inflammatory drug (NSAID) has poor aqueous solubility. The present study describes the complexation of NM with β-cyclodextrin (β-CD) and its derivative hydroxypropyl β-cyclodextrin (HPβ-CD). The complexation was studied by phase solubility method, Fourier transformed infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffractometry (XRD). The complexes were prepared by a freeze-drying technique. The in vitro dissolution rate of drug-HPβ-CD complex was faster compared to the drug-β-CD complex and drug alone.     

Inclusion complexes of fluorofenidone with β-cyclodextrin and hydroxypropyl-β-cyclodextrin

Background: Fluorofenidone is a novel antifibrotic drug and its aqueous solubility is low. Aim: This study was to prepare and characterize inclusion complexes of fluorofenidone (AKF-PD) with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). Method: The AKF-PD/cyclodextrins (CDs) inclusion complexes were prepared by coprecipitation and freeze-drying, respectively. The solubility enhancement of AKF-PD was evaluated by phase solubility method. Inclusion complexation in solid phase was studied by X-ray diffraction (XRD) and differential thermal analysis (DTA). The dissolution profiles of AKF-PD/CDs inclusion complexes were investigated and compared with those of their physical mixtures and AKF-PD alone. Results: The phase solubility diagrams of AKF-PD with β-CD and HP-β-CD were of A_L-types, and the solubility of AKF-PD could be increased by 51.5% for β-CD at 0.014 M and 794.0% for HP-β-CD at 0.254 M. The results from XRD and DTA suggested that AKF-PD could form inclusion complex with β-CD or HP-β-CD. The dissolution rate of AKF-PD from the inclusion complexes was much more rapid than AKF-PD alone. Conclusions: The formulation of AKF-PD/CDs inclusion complexes showed superior performance in improving dissolution properties of AKF-PD.     

Etodolac and Solid Dispersion with P-Cyclodextrin

Etodolac/β-cyclodextrin (Eto/β-CD) dispersions were prepared with a view to study the influence of β-CD on the solubility and dissolution rate of this poorly soluble drug. Two systems were used: physicai mixture of Eto/β-CD and kneading solid dispersion of Eto/β-CD. Physical characterization of the prepared systems was carried out by scanning electron microscopy (SEM), differential scanning calorimetric (DSC), x-ray, and IR studies. The solubility and dissolution rate of Eto were increased with β-CD physical mixture as well us with Eto/β-CD kneading solid dispersion. However, enhancement was not statistically different among various cyclodextrin dispersions.     

Study of Surfactants/β-Cyclodextrin Interactions Over Mequitazine Dissolution

Surfactant/β-cyclodextrin interactions were investigated by studying the dissolution of mequitazine in different binary (aqueous solutions of β-CD or surfactants) and ternary (aqueous solution of β-CD and surfactants) dissolution media. Results were compared with those obtained from binary media with 50, 250, and 500 mg of surfactants (preceding paper). Results show that there is an interaction between β-cyclodextrin and surface-active agent, and that the type and extent of interaction are controlled by the nature and the amount of the surface-active agent. A decrement in drug dissolution rate was obtained from all of the ternaly media containing β-cyclodextrin and sodium lauryl sulfate as surfactant in the ratio of 1:1 mol/mol. These facts suggest that sodium lauryl sulfate and β-cyclodextrin form an inclusion compound in the molecular ratio of 1:1.     

Adsorption of reactive dyes from aqueous solutions by fly ash: kinetic and equilibrium studies

Adsorption kinetic and equilibrium studies of three reactive dyes namely, Remazol Brillant Blue (RB), Remazol Red 133 (RR) and Rifacion Yellow HED (RY) from aqueous solutions at various initial dye concentration (100–500 mg/l), pH (2–8), particle size (45–112.5 μm) and temperature (293–323 K) on fly ash (FA) were studied in a batch mode operation. The adsorbent was characterized with using several methods such as SEM, XRD and FTIR. Adsorption of RB reactive dye was found to be pH dependent but both RR and RY reactive dyes were not. The result showed that the amount adsorbed of the reactive dyes increased with increasing initial dye concentration and contact time. Batch kinetic data from experimental investigations on the removal of reactive dyes from aqueous solutions using FA have been well described by external mass transfer and intraparticle diffusion models. It was found that external mass transfer and intraparticle diffusion had rate limiting affects on the removal process. This was attributed to the relatively simple macropore structure of FA particles. The adsorption data fitted well with Langmuir and Freundlich isotherm models. The optimum conditions for removal of the reactive dyes were 100 mg/l initial dye concentration, 0.6 g/100 ml adsorbent dose, temperature of 293 K, 45 μm particle size, pH 6 and agitation speed of 250 rpm, respectively. The values of Langmuir and Freundlich constants were found to increase with increasing temperature in the range 135–180 and 15–34 mg/g for RB, 47–86 and 1.9–3.7 mg/g for RR and 37–61 and 3.0–3.6 mg/g for RY reactive dyes, respectively. Different thermodynamic parameters viz., changes in standard free energy, enthalpy and entropy were evaluated and it was found that the reaction was spontaneous and endothermic in nature.     

Gefitinib–cyclodextrin inclusion complexes: physico-chemical characterization and dissolution studies

Background: Gefitinib, an anticancer drug, has an extremely low aqueous solubility, and its oral absorption is limited by its dissolution rate. The solubility and dissolution of gefitinib can be improved by complexation with cyclodextrins (CDs). Methods: Phase solubility studies of gefitinib with hydroxypropyl βCD (HPβCD) and randomly methylated βCD (RMβCD) in n various aqueous systems was conducted to characterize the complexes in the liquid state. The inclusion complexes in the solid state were prepared by freeze-drying method and characterized by X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC). Results: Gefitinib formed stable complexes with HPβCD and RMβCD in distilled water as indicated by the association rate constants (Ks) of 458.9 and 1096.2 M^?1 for HPβCD and RMβCD, respectively. The complexation of gefitinib with CDs in pH 4.5 acetate buffer indicated an A_N type of phase-solubility diagrams, whereas gefitinib and HPβCD in distilled water in the presence of polymers such as polyvinyl pyrrolidone K-30 (PVP) or hydroxypropyl methylcellulose E3 (HPMC) resulted in A_P-type phase-solubility diagrams. The solid-state amorphous complexes (as described by DSC and X-RD) showed substantial increases in the solubility and dissolution rate of gefitinib with both CDs. Further increases in the solubility and dissolution rate of the gefitinib-HPβCD freeze-dried complex were obtained by physically mixing the complex with PVP and HPMC. Conclusion: Gefitinib formed stable inclusion complexes with HPβCD and RMβCD, and the solubility and dissolution rate of the drug was significantly increased.     

Preparation and properties of TiN and AlN films from alkoxide solution by thermal plasma CVD method

Single phase TiN and AlN films were prepared on a Si wafer from titanium tetra-etoxide and aluminum tri-butoxide solutions dissolved in ethanol and toluene, respectively, using an Ar/N₂/H₂ radio-frequency (r.f.) inductive thermal plasma chemical vapor deposition (CVD) method. The films were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, measurement of electrical resistivity and Vickers microhardness. Factors affecting the formation of the films (lattice parameter, chemical composition, oxygen/carbon content, and deposition rate of the films) were examined in terms of the N₂ flow rate (2.5–4.5 slm), substrate temperature (300–700°C), feed rate of the solution (0.025–0.3 ml/min), and the mole ratio of the alkoxide solution (1:1–1:3). The optimum conditions for preparation of TiN films produced a film 0.2–3 μm thick with an oxygen content of 8 at.% and a free carbon content of 4 at.%, showing an electrical resistivity of 370 μΩ cm. The optimum conditions for AlN films produced a film 0.3 μm thick containing 14 at.% oxygen and 8 wt.% carbon. The deposition rate of the TiN film was determined to be 30–35 nm/min. The Vickers microhardness of the TiN and AlN films was found to be 10±1 and 13±3 GPa, respectively.     

Investigation of nanostructured lipid carriers for transdermal delivery of flurbiprofen

The aim of this study was to develop nanostructured lipid carriers (NLC) for transdermal delivery of Flurbiprofen (FP). The physical stability of FP-NLC and its in vitro permeation profile were investigated. After three months of storage at 4°C, 20°C, and 40°C, no significant differences between the evaluated parameters, such as pH value, the entrapment efficiency, particle size, and zeta potential were observed. In in vitro permeation studies, the cumulative permeated amounts and the release rate from FP-NLC were 412.53 ± 21.37 μg/cm² and 35.25 μg/cm²/h after 12 h (n = 6), respectively, while from saturated FP-PBS (pH = 7.4) were 90.83 ± 8.67 μg/cm² and 6.99 μg/cm²/h, respectively. These results indicated that the FP-NLC were with good physical stability and were able to improve the permeated amounts and the release rate of FP. It could potentially be exploited as a carrier with improved drug entrapment efficiency and permeated amount in the transdermal delivery of FP.     

Enhancement of Solubility, Dissolution Rate, and Oral Bioavailability of Rs-82856 by Complex Formation with Cyclodextrins

RS-82856 is a new inotropic agent for treatment of congestive heart failure. Oral bioavailability was found to be very poor likely due to insufficient aqueous solubility (∼ 4.4 mcg/ml) and slow dissolution rate. Inclusion complexes with cyclodextrins were shown to enhance the solubility, dissolution rate and thereby oral bioavailability of the drug. Maximum solubilities of the drug complexes with alpha-, beta-, and gamma-cyclodextrin were 14, 30 and 55 times, respectively, more soluble than the uncomplexed drug. Phase solubility studies revealed a 1:l complexation constant of 136.5, 370.4, and 64.7 for alpha -, beta - and gamma-cyclodextrin complexes, respectively . The complexation between beta-cyclodextrin and the drug is apparently the strongest among the three cyclodextrins. Dissolution profiles of the beta-cyclodextrin complex indicated a dramatic increase in dissolution rate compared to that of the drug. However,a physical mixture of the beta-cyclodextrin and the drug gave an identical dissolution profile to that of the drug.The beta-cyclodextrin complex of the drug dissolves 90% with in 20 minutes while the free based is solves 25% with in the same time interval in water. In an acidic medium (ph 1.5) the beta-cyclodextrin complex and the free based is solve 90% and 30% respectively within 10 minutes.In asingle dose cross-over study in three dogs,the bioavailability of the beta-cyclodextrin complex was found to improve greatly over that of the drug. An increased C_max (2.5 times),and an increased AUC (2.5 times) were observed with the beta-cyclodextrin complex compared to the drug.     

Liposome Delivery Systems Containing Ibuprofen

Multilamellar liposome vescicles containing ibuprofen were successfully prepared by hydrating the lipids in the presence of organic solvent. The effects of varying the ratio of lipid to drug; the filter size; and the stirring period during hydration of the dried lipids layer were evaluated. Liposomes sample prepared by using a ratio of 3 lipid: 1 drug gave the highest entrapment efficiency of the drug and released all the drug over 12 hours of testing dissolution. Also the dissolution data showed that the drug release from large liposomes (5.0 μm) was 65.7% after 12 hours; 62.6% from medium size (0.8 pm) and 46.6% from small size liposomes (0.22 μm). Additionally, the increase of the stirring period during hydration of the dried lipid layer with the aqueous phase increased the release of the drug from the liposomes.     

Elaboration, microstructure and reactivity of Cr3C2 powders of different morphology

Cr₃C₂ powders have been prepared by heat-treatment of metastable chromium oxides of controlled morphology in H₂---CH₄ atmosphere. Starting with these highly reactive oxides allows formation of Cr₃C₂ at 700 °C. The reaction is pseudomorphic and different grain shapes (needles, rods, spheres and polyhedra) have been obtained. The size distribution is narrow and the grain size is generally of the order of a few tens of micrometers, but the “spheres” are in fact made up of aggregates of small platelets about 1.5 μm wide and 0.7 μm thick. The oxidation in air of the carbides was studied by thermal analyses (TGA, DTG and DSC) and was found to proceed in four steps in the 250–700 °C range. The differences observed between the carbides are related to their morphology and texture.