The Effect of Poloxamer Viscosity on Liquid-Filling of Solid Dispersions in Hard Gelatin Capsules

ABSTRACT

Preliminary studies were undertaken on poloxamers to investigate their suitability for liquid-fill formulations for hard gelatin capsules. Poloxamers with viscosity in the range (0.32–2.8 Pa s) and melting point 48–58°C were used as the continuous phase, with α-lactose monohydrate of negligible solubility in the molten poloxamers, as a model insoluble disperse phase. Physicochemical characterization by rheology, melt solidification and moisture uptake indicated that poloxamers were suitable excipients for liquid-filling in hard gelatin capsules. 10% w/w lactose/poloxamer dispersions were thixotropic and shear thinning and exhibited good capsule-filling properties, disperse-phase uniformity and satisfactory apparent viscosity at 70°C.     

Physical and chemical characterization of thermosoftened bases for molten filled hard gelatin capsule formulations

Dynafill, Dynasan-114, Lutrol-F68, PEG-10000 and PEG-20000 have been examined as potential bases for the preparation of fusion formed solid dispersions for molten filling into hard gelatin capsules. Investigations included, an examination of thermal effects on crystal structure by DSC and XRD, a theological study to evaluate capsule filling characteristics, dissolution studies on drug/base formulations, chemical analysis for free fatty acid impurities in Dynafill and Dynasan-114, and detailed studies on selected drug/base formulations. PEG-20000 and Dynasan-114 were not examined in detail, after preliminary investigations had shown high viscosity and poor filling characteristics for PEG-20000 and poor dissolution characteristics for Dynasan-114. Dynafill provided good release profiles when formulated with a variety of model drugs (Acetohexamide, Ibuprofen, Indomethacin, Quinidine sulphate and Theophylline). Results from hot stage photomicrography supported by DSC and XRD were used to construct a phase diagram of the Ibuprofen/Lutrol-F68 system. The evidence from the phase diagram indicated the formulation of a simple eutectic system with no solid solubility and a eutectic composition at approximately 35% w/w Ibuprofen.     

Physical and chemical characterization of thermosoftened bases for molten filled hard gelatin capsule formulations

Abstract

Dynafill, Dynasan-114, Lutrol-F68, PEG-10000 and PEG-20000 have been examined as potential bases for the preparation of fusion formed solid dispersions for molten filling into hard gelatin capsules. Investigations included, an examination of thermal effects on crystal structure by DSC and XRD, a theological study to evaluate capsule filling characteristics, dissolution studies on drug/base formulations, chemical analysis for free fatty acid impurities in Dynafill and Dynasan-114, and detailed studies on selected drug/base formulations. PEG-20000 and Dynasan-114 were not examined in detail, after preliminary investigations had shown high viscosity and poor filling characteristics for PEG-20000 and poor dissolution characteristics for Dynasan-114. Dynafill provided good release profiles when formulated with a variety of model drugs (Acetohexamide, Ibuprofen, Indomethacin, Quinidine sulphate and Theophylline). Results from hot stage photomicrography supported by DSC and XRD were used to construct a phase diagram of the Ibuprofen/Lutrol-F68 system. The evidence from the phase diagram indicated the formulation of a simple eutectic system with no solid solubility and a eutectic composition at approximately 35% w/w Ibuprofen.     

The effect of poloxamer viscosity on liquid-filling of solid dispersions in hard gelatin capsules

Preliminary studies were undertaken on poloxamers to investigate their suitability for liquid-fill formulations for hard gelatin capsules. Poloxamers with viscosity in the range (0.32-2.8 Pa s) and melting point 48-58 degrees C were used as the continuous phase, with alpha-lactose monohydrate of negligible solubility in the molten poloxamers, as a model insoluble disperse phase. Physicochemical characterization by rheology, melt solidification and moisture uptake indicated that poloxamers were suitable excipients for liquid-filling in hard gelatin capsules. 10% w/w lactose/poloxamer dispersions were thixotropic and shear thinning and exhibited good capsule-filling properties, disperse-phase uniformity and satisfactory apparent viscosity at 70 degrees C.     

The use of Thermal Analysis in the Study of Solid Dispersions

Abstract

Differential thermal analysis (DTA) has been used to study the properties of seven drug-polyethylene glycol 6000 solid dispersions immediatley after preparation by rapid cooling. PEG 6000 displayed a melting point of 64°C but other, second order transitions occurred at 29 to 40°C and at ～ -50°C. Melts of chloramphenicol, glutethimide, griseofulvin, indomethacin and paracetamol solidifed to glasses, but phenacetin and phenylbutazone recrystallised. By examining the dispersions at various drug:PEG 6000 ratios, ranges were estimated which corresponded to PEG recrystallisation, PEG fusion, drug recrystallisation and drug fusion. It was predicted that systems which displayed PEG melting endotherms at drug contents of 0 to > 70% drug and drug melting endotherms at contents in excess of 50% drug, made unsuitable solid dispersions because increases in dissolution rate occurred over a limited range of low drug content. Graphs of reciprocal glass transition temperatures (T_g) and dispersion content indicated a transition temperature for PEG 6000 at -71°C. Using this value and the observed T_g values of the drugs, estimates of T- values were compared with observed values throughout the drug:PEG 6000 phase diagrams. Systems where the observed T_g values were higher than calculated T_g values (paracetamol or chloramphenicol) were less prone to age-mediated dissolution changes than those systems where the calculated T_g values exceeded the observed values (glutethimide, griseofulvin or indomethacin).     

Biopharmaceutical Study of Glybornuride-Polyethylene Glycol Systems

Glybornuride is an oral hypoglucaemiant drug which exhibits a very low water solubility. Consequently,the solid dispersions of this drug with PEG 6,000; 10,000 and 20,000 have studied. According to the phase diagrams obtained, the following solid dispersions of glybornuride were prepared: at 30% with PEG 6,000 and 10,000 and 40% with PEG 20,000.Dissolution curves show that glybornuride dissolves faster as solid dispersion, particularly with PEG 6,000. The administration of glybornuride as a solid dispersion into rabbits induced a faster decrease of glucaemia levels than a physical mixture with polyethylene-glycols.     

水性聚氨酯防水涂膜材料的制备与性能

为了研究多元醇类型对水性聚氨酯防水涂膜材料性能的影响,选用分子量均为1 000的聚酯型、聚醚型多元醇为软段,通过预聚体法制备了一系列水性聚氨酯(WPU)分散体;探讨了WPU的粒径、黏度、结构及结晶性、水抵抗性能。结果表明:制备的WPU分散体粒径较小;聚酯多元醇型[聚己二酸乙二醇酯(PB)、聚碳酸酯(PCL)]WPU膜的拉伸强度、结晶性能高于聚醚多元醇型[聚丙二醇(PPG)、聚四氢呋喃醚二醇(PTMG)]的,但是断裂伸长率低于聚醚多元醇型的WPU膜;其中PTMG型WPU膜的水接触角最大,达到66.5°,吸水率最小(6.2%),防水性最佳,综合性能最好,最适合用作环境友好型纤维织物防水涂膜材料。     

Washcoating of low surface area cerium oxide on complex geometry substrates

ABSTRACT

An acid-free formulation based on water, glycerol, and polyvinyl alcohol (PVA) was studied to disperse and stabilize, via steric-like interaction, low surface area cerium oxide powders. A dispersion route that implies a milling process and a proper ratio among the components was experienced. PVA was used as viscosity modulator, to enhance viscosity and system stability. Newtonian fluids, suitable for foams dip-coating, were obtained in the application shear range. Foams with different porosities (20, 30, and 40 pore per inch density) were coated. It was found that withdrawal velocity did not affect deposition: a constancy in coating load was obtained once rheology was fixed, while multiple dipping was effective to enhance load. An optimal flash drying temperature (350°C) was identified to consolidate the coated layer and to decompose the organic additives. Good loads, homogeneous coverage, and no pore clogging were obtained after calcination at 900°C. Even though acceptable weight losses were obtained, further investigations need to be accomplished to understand data scattering after adhesion tests.     

Synthesis and Characterization of PEG-Sr Hexaferrite by Sol–Gel Conversion

Sr-M-type hexagonal ferrites have been prepared via a sol?Cgel route, and the effects of addition of different molecular weight polyethylene glycol (PEG) into the sol solutions on the static magnetic properties and particle morphology have been studied. Crystalline phases of the samples were determined by XRD analysis. FT-IR and TG analyses were used to prove the presence of PEG on SrFe₁₂O₁₉. The results showed that adding PEG with different molecular weight into the sol solutions affected the formation mechanism of SrFe₁₂O₁₉. Sr-M precursors prepared by various PEG types show different magnetic behaviors after pre-calcination at 150?^°C. This discrepancy is explained by the formation of a different phase during the synthesis of SrM particles.     

Study of viscosity and specific heat capacity characteristics of water-based Al2O3 nanofluids at low particle concentrations

In this paper, the specific heat capacity and viscosity properties of water-based nanofluids containing alumina nanoparticles of 47 nm average particle diameter at low concentrations are studied. Nanofluids were prepared with deionised water as base fluid at room temperature by adding nanoparticles at low volume concentration in the range of 0.01%–1% to measure viscosity. The effect of temperature on viscosity of the nanofluid was determined based on the experiments conducted in the temperature range of 25°C to 45°C. The results indicate a nonlinear increase of viscosity with particle concentration due to aggregation of particles. The estimated specific heat capacity of the nanofluid decreased with increase of particle concentration due to increase in thermal diffusivity. Generalised regression equations for estimating the viscosity and specific heat capacity of nanofluids for a particular range of particle concentration, particle diameter and temperature are established.     

Retardation of Polymeric Carrier Dissolution by Dispersed Drugs: Factors Influencing the Dissolution of Solid Dispersions Containing Polyethlene Glycols

Molecular weight is an important determinant of plyethylene glycol (PEG) dissolution rate: the rate decreasing as the molecular weight is increased. PEG samples of equivalent nominal. molecular weight had different dissolution properties. Intrinsic viscosity and differential scanning calorimetry suggested that the observed differences my be related to molecular weight variation between samples. The dissolution rate of PEG from solid dispersions is retarded, the effect being dependent on the chemical nature of the drug and its concentration. Phenobarbitone was particularly potent in retarding PEG dissolution. Phenobarbitone dissolution rate was retarded from dispersions of high phenobarbitone content. However drug dissolution from solid dispersions low in phenobarbitone were greater than that of pure phenobarbitone. The low dissolution rates were explained in terms of formation of the 2:1 PEG monomer: phenobarbitone complex during solid dispersion formation. At high PEG weight fractions (i.e. 30:1, 50:1) drug dissolution was carrier controlled and although PEG dissolution was greatly suppressed, it was sufficiently large to transport the drug into solution at a rate greater than that of pure phenobarbitone.     

Retardation of Polymeric Carrier Dissolution by Dispersed Drugs: Factors Influencing the Dissolution of Solid Dispersions Containing Polyethlene Glycols

Molecular weight is an important determinant of plyethylene glycol (PEG) dissolution rate: the rate decreasing as the molecular weight is increased. PEG samples of equivalent nominal. molecular weight had different dissolution properties. Intrinsic viscosity and differential scanning calorimetry suggested that the observed differences my be related to molecular weight variation between samples. The dissolution rate of PEG from solid dispersions is retarded, the effect being dependent on the chemical nature of the drug and its concentration. Phenobarbitone was particularly potent in retarding PEG dissolution. Phenobarbitone dissolution rate was retarded from dispersions of high phenobarbitone content. However drug dissolution from solid dispersions low in phenobarbitone were greater than that of pure phenobarbitone. The low dissolution rates were explained in terms of formation of the 2:1 PEG monomer: phenobarbitone complex during solid dispersion formation. At high PEG weight fractions (i.e. 30:1, 50:1) drug dissolution was carrier controlled and although PEG dissolution was greatly suppressed, it was sufficiently large to transport the drug into solution at a rate greater than that of pure phenobarbitone.     

Experimental investigation on thermophysical properties of solar glycol dispersed with multi-walled carbon nanotubes

This article deals with well-dispersed solar glycol-based nanofluids containing multi-walled carbon nanotube (MWCNT) nanoparticles with different particle volume concentrations of 0.1%, 0.2%, 0.3%, and 0.4% prepared by typical two-step method. Thermal conductivity, viscosity and specific heat capacity of solar glycol (SG)-based MWCNT nanofluids, in the temperature range of 30°C–70°C were measured. The values of density showed a noticeable deviation from the predictions of Pak and Cho correlation. Hence, correlations are developed for thermal conductivity and viscosity from the experimental results obtained from the various range parameters of interest. The presence of MWCNT enhanced the thermal conductivity of the nanofluids by 17.26% at 0.4 vol.% particle concentration at 70°C. The relative viscosity of MWCNT nanofluids depends on the nanoparticles percentage concentration and decreases significantly with increase in temperature for higher concentrations. The presence of MWCNT enhances the specific heat of the nanofluids significantly, and this enrichment decreases with the increase of the MWCNT concentration. MWCNT/SG represents a new and innovative class of heat-transfer fluid, which possesses excellent thermophysical properties. The MWCNT/SG-based nanofluids could be suitable working fluids for solar thermal and automobile applications.     

The rheological properties and characterization of bentonite dispersions in the presence of non-ionic polymer PEG

The effect of poly(ethylene glycol) on the flow behavior of Ca-bentonite and soda activated bentonite dispersions was characterized by the plastic viscosity, the relative viscosity and the yield values. In the range 0.025–12.5 mol/m³, poly(ethylene glycol) (PEG400, PEG3000, PEG8000) was added to bentonite-water systems in different concentrations. Three layered phases with different basal spacings for each Ca- and Na-bentonites were obtained, as shown by XRD studies. The maximum swelling had a basal spacing at 1.82 nm for both PEG400 containing Ca- and Na-bentonites. In addition, expanded basal spacings are displayed at 1.91 nm for Ca- and 2.08 nm for PEG8000 containing Na-bentonites. After the PEG addition, some significant changes in rheological properties were observed; corresponds changes were also found during XRD and IR studies. The results are interpreted according to the type of bentonites, molecular weight of PEG and their concentrations.     

Enhancement of Dissolution of Ethopropazine Using Solid Dispersions Prepared with Phospholipid and/or Polyethylene Glycol

The purpose of this study was to improve the dissolution properties of a poorly water soluble and bioavailable drug, ethopropazine HCl (ET), by incorporating the drug in three different types of solid dispersion systems. Solid dispersions of ET were prepared using 1:1 (w/w) ratios of (1) phospholipid (1,2 dimyristoyl-sn-glycerophosphocholine) (DMPC), (2) polyethylene glycol 8000 (PEG8000), and (3) a novel combination of both DMPC and PEG8000. Using the solvent method of preparation, ET and DMPC and/or PEG were dissolved in chloroform, and solvent subsequently was evaporated using nitrogen gas. The resulting solid dispersion(s) was passed through a 60-mesh sieve. Characterization of ET/DMPC solid dispersion was performed by differential scanning calorimetry (DSC) and X-ray diffractometry studies. Dissolution studies conducted in phosphate buffered saline (PBS) (pH 7.4, 37°C ± 0.5°C) using the USP type II (paddle) dissolution apparatus showed significant increases in the dissolution rate of ET with all the solid dispersions in this study. Specifically, within the first 5 min (D5), solid dispersions containing ET/DMPC (1:1) showed an eightfold increase in dissolution; in combination with DMPC and PEG8000 (1:1), there was an approximately sixfold increase; and a fourfold increase was observed with PEG8000 (1:1). Complete dissolution of all solid dispersions occurred within 60 min (D60) of the run. Storage of the ET/DMPC sample for over 4.5 months revealed a decrease in the dissolution rate when compared to freshly prepared sample. Overall, it was concluded that the dissolution rate of ET significantly improved when dispersed in all the selected carrier systems. However, the solid dispersion of ET/DMPC was observed to be superior to the other combinations used.     

Thermal Behavior and Dissolution Properties of Naproxen From Binary and Ternary Solid Dispersions

Solid dispersions of 10% w/w naproxen (NAP) in poly(ethylene glycol) (PEG) (4000, 6000, or 20,000) as a carrier with or without incorporation of anionic (sodium dodecyl sulfate; SDS) or nonionic (Tween 80; Tw80) surfactant were prepared by the melting method. Physicochemical characteristics were determined by differential scanning calorimetry (DSC) and X-ray diffraction analysis. The results of dissolution studies showed that drug dissolution properties were better from ternary systems than from binary systems since in the former the wetting and solubilizing effects of surfactant and polymer were additive. No influence of the PEG molecular weight was found. The best performance given by anionic surfactant has been attributed to several factors, such as higher hydrophilicity, better solubilizing power, and most facile interaction with both drug and PEG. No important changes in solid-state characteristics or in drug dissolution properties were found after 30 months storage for dispersions with or without surfactant. Only a slight decrease in initial drug dissolution rate was observed at the highest concentration (10% w/w) of SDS.     

Thermal behavior and dissolution properties of naproxen from binary and ternary solid dispersions

Solid dispersions of 10% w/w naproxen (NAP) in poly(ethylene glycol) (PEG) (4000, 6000, or 20,000) as a carrier with or without incorporation of anionic (sodium dodecyl sulfate; SDS) or nonionic (Tween 80; Tw80) surfactant were prepared by the melting method. Physicochemical characteristics were determined by differential scanning calorimetry (DSC) and X-ray diffraction analysis. The results of dissolution studies showed that drug dissolution properties were better from ternary systems than from binary systems since in the former the wetting and solubilizing effects of surfactant and polymer were additive. No influence of the PEG molecular weight was found. The best performance given by anionic surfactant has been attributed to several factors, such as higher hydrophilicity, better solubilizing power, and most facile interaction with both drug and PEG. No important changes in solid-state characteristics or in drug dissolution properties were found after 30 months storage for dispersions with or without surfactant. Only a slight decrease in initial drug dissolution rate was observed at the highest concentration (10% w/w) of SDS.     

Improved stability of solid dispersions of manidipine with polyethylene glycol 4000/copovidone blends: application of ternary phase diagram

Context: Manidipine (MDP) is generally used clinically as an antihypertensive agent; however, the bioavailability of orally administered MDP is limited due to their very low water solubility.

Objective: The objectives of this research were, therefore, to increase the solubility of MDP by the formation of ternary solid dispersions (tSD) with polyethylene glycol 4000 (PEG4000) and copovidone and to improve their stability.

Methods: Solid ternary phase diagram was constructed to find homogeneous solid dispersion region after melting and solidifying at low temperature with different quenching substances. The pulverized powder of solid dispersions was then determined, for their physicochemical properties, by differential scanning calorimetry, powder X-ray diffractometry, Fourier transform infrared (FTIR) spectroscopy and hot stage microscopy. The solubility and dissolution of MDP from the tSD were investigated. The physical stability of tSD was also determined under accelerated condition at 40?°C/75% relative humidity (RH) for 6 months.

Results and discussion: The results showed that MDP was molecularly dispersed in PEG4000 and copovidone when the tSD was created from homogeneous region of solid ternary phase diagram. FTIR results confirmed that strong hydrogen bonding was presented between MDP and copovidone, leading to a significant increase in the solubility and dissolution of MDP. After storage at accelerated condition (40?°C/75%RH) for 6 months, the tSD still showed a good appearance and high solubility.

Conclusion: The results of this study suggest that tSD prepared by melting has promising potential for oral administration and may be an efficacious approach for improving the therapeutic potential of MDP.     

Effect of the molecular weight of polyethylene glycol as single additive in copper deposition for interconnect metallization

Void-free deposition for integrated circuit interconnect with polyethylene glycol (PEG) as the single additive has been developed based on the characteristics of the current-potential responses at an acid copper sulfate bath containing PEG and chloride ions (Cl⁻). Several electrochemical methods were employed, including chronopotentiometry, linear sweep voltammetry and cyclic voltammetry to study the effect of PEG molecular weight on adsorption behaviors and suppression ability of PEG. Field emission scanning electron microscopy was utilized for the characterization of microstructural evolution, related with the suppression ability. The filling capabilities were carried out using acid copper baths containing PEG at various molecular weights, ranging from 3200 to 20,000g mol^− 1. Better filling capacity can be obtained as the molecular weight of PEG increases.     

The MiniWiD-Coater. III. Effect of Application Temperature on the Dissolution Profile of Sustained-Release Theophylline Pellets Coated with Eudragit Rs 30 D

Abstract

Theophylline pellets were coated with Eudragit RS 30 D in a miniature fluid-bed pan coater called MiniWiD developed recently. The dispersions were plasticized with varying amounts of triethyl citrate (TEC), dibutyl phthalate (DBP), and polyethylene glycol 6000 (PEG) and applied at different temperatures ranging from 25 to 45 °C. Theophylline release was tested by dissolution using the USP Apparatus 2 (paddle) in 0.1 N hydrochloric acid under sink conditions over 6 hours.

At a coating level of 4 % (0.7 mg/cm²) sustained-release profiles were obtained from dispersions plasticized with TEC or DBP. By reducing the amount of plasticizer from 20 to 10%, films with higher permeabilities were obtained. This effect was compensated by tempering the pellets at 50 deg;C for 24 hours. The coating temperature had little effect on the dissolution profiles of TEC-plasticized films and no effect on films with DBP.

Coatings plasticized with 20% PEG were applied at temperatures ranging from 25 to 45 °C. These films required a coating level of about 18 % (3.3 mg/cm²) to provide comparable sustained-release properties. In contrast to DBP and TEC, a strong influence of the coating temperature on the release rates was observed in which higher temperatures led to slower release rates. This behavior can be explained by the minimum film-forming temperature (MFT). Since PEG does not lower the MFT of Eudragit RS 30 D, the application of these films below the MFT of 45 °C is associated with a lower degree of film formation.