Nonsolvent Solvent Research Articles

Precipitation and Condensation of Organic Particles

The precipitation and condensation of submicron organic particles are reviewed. The importance of physical state effects is discussed, and the role of compartmentalization in controlling particle size is introduced. The thermodynamic driving forces for precipitation and phase transformation are briefly reviewed. The use of emulsification as a primary step in producing small particle dispersions is described and illustrated with photographic and pharmaceutical applications. Precipitation driven by solvent shifting is illustrated and applications in preparing organic–inorganic composites and protein coacervation are described. Miscible solvent–nonsolvent induced precipitation is outlined, and followed by related applications using supercritical fluid technology. The special case of solvent shifting, pH shifting, is reviewed at length and illustrated to be effective for preparing nanoparticles of organics having weak acid functional groups. The first applications of organic particle precipitation in reverse microemulsion systems are described. The applicability of gas condensation methods is illustrated. Exciting new applications of precipitation in submicron hollow spheres and dye entrapment in submicron polymer gel networks are discussed.

Calculation of alcohol‐acetone‐cellulose acetate ternary phase diagram and their relevance to membrane formation

AbstractABSTRACTAlcohol‐acetone‐cellulose acetate phase diagrams incorporated with methanol, ethanol, and isopropanol as nonsolvents are calculated according to a new form of the Flory–Huggins equation. Nonsolvent–cellulose acetate interaction parameters are measured by swelling experiments. Concentration‐dependent nonsolvent–solvent interaction parameters are obtained by vapor–liquid equilibrium and the Wilson equation. It is shown that alcohol is a week coagulant compared with water, and water > methanol > ethanol > isopropanol for cellulose acetate. The phase diagrams characteristic of acetone‐cellulose acetate combined with water, methanol, ethanol, and isopropanol as nonsolvents is different, which leads to the different morphological structure of a cellulose acetate membrane. The structure of a water coagulated membrane has large macrovoids from liquid–liquid phase separation. A methanol coagulated membrane has a honeycomb‐like structure from spinodal microphase separation. An ethanol or isopropanol coagulated membrane has a thicker, dense top layer from the delay time phase separation. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 1650–1657, 2001

The formation mechanism of membranes prepared from the nonsolvent–solvent–crystalline polymer systems

Two different types of membranes were prepared by immersion–precipitation process in two nonsolvent–DMSO–poly(ethylene-co-vinyl alcohol) (EVAL) systems. The effect of nonsolvent on the resulting membrane structure was studied via scanning electron microscopy. On using 2-propanol as the nonsolvent, the membrane showed a homogeneous particulate morphology. If the nonsolvent was changed to water, the membrane structure was a typically asymmetric structure while the particulate morphology was suppressed. In order to understand the change of the obtained membrane structures, the phase diagrams of water–DMSO–EVAL and 2-propanol–DMSO–EVAL systems were contrasted at 25°C. Both crystallization-induced gelation and liquid–liquid demixing were observed and equilibrium crystallization lines are always positioned above the binodal boundaries. Moreover, the precipitation rate of the EVAL solution in 2-propanol and water were examined by the light transmission experiments and the local composition profiles of membrane solution during membrane formation were analyzed by using a ternary mass transfer model. Based on both thermodynamic behaviors and kinetic properties, the membrane structures obtained were discussed in terms of the sequence and mechanism of phase transformations during membrane formation.

The formation mechanism of membranes prepared from the crystalline EVAL polymer–water (nonsolvent)–2-propanol (nonsolvent) system

Crystalline poly(ethylene–co–vinyl alcohol) (EVAL) membranes from the water–2-propanol cosolvent were prepared by immersion–precipitation at 60°C. The use of two nonsolvents serving as a cosolvent system, replacing the traditional solvent–nonsolvent pair, for the membrane formation was investigated. The two-nonsolvent proportion in which they are mixed to produce the cosolvent system and the prediction of the membrane structures were based on the complex ternary phase diagram at 60°C. It was attempted to relate the influence of liquid–liquid demixing and solid–liquid demixing on the membrane morphologies to the ternary phase diagram. Two different morphologies and two different demixing rates could be obtained by using water and 2-propanol, respectively, to precipitate the cosolvent system. When water was used as the precipitation medium, it showed a rapidly precipitating system and cellular morphologies were obtained due to liquid–liquid demixing. In contrast, when 2-propanol was used as the precipitation medium, it showed delayed demixing and crystallization-induced particulate morphologies were formed. Trends expected on the basis of the phase diagram was in reasonable agreement with the observed membrane morphology. Therefore, the principles of membrane formation established for the ternary systems with nonsolvent–solvent–polymer can be extended to a nonsolvent–nonsolvent–polymer system.

MICROENCAPSULATION OF ALLOPURINOL USING A FULLY IMPROVED NON-SOLVENT ADDITION TECHNIQUE AND A NOVEL BINARY BLEND BASED ON POLYVINYL CHLORIDE: FACTORIAL DESIGN APPLICATION

A fully improved non-solvent addition coacervation-phase separation process which utilizes tetrahydrofurfuryl alcohol – cyclohexane : hexane (1:1 v/v ratio) as a solvent-non solvent pair, a novel binary blend comprising of polyvinyl chloride in combination with poloxamer 188 [a triblock copolymer of poly (ethylene oxid) – poly (propylene oxide) – poly (ethylene oxide)] as the wall material and ethylene-vinylacetate copolymer or polyisobutylene as coacervation-inducing agents has been developed for encapsulating allopurinol. The role of the coaddition of dioctylphthalate as a plasticizer and poloxamer 188 as a complementary coating polymer to the polymer solution phase on the properties of the microcapsules was investigated. The results indicated that plasticized / blended microcapsules resulted in a great shift to a narrow particle size distribution and a significant reduction in the drug loss percentage and the drug release rate in comparison with unplasticized / unblended microcapsules or plasticized polyvinyl chloride microcapsules. In the preparation of the plasticized / blended microcapsule formulations, a 23 full factorial design based on three independent variables viz.; polymers blend concentration, amount of allopurinol and the type of the coacervation-inducing agent was applied. The mean influences of these variables on the micromeritic parameters (geometric mean particle diameter, span value and drug content) and dissolution properties of the microcapsules were characterized quantitatively and represented by predictor polynomial equations. The kinetic model according to the Rosin-Rimmler-Sperling-Bennett-Weillbull (RRSBW) distribution was applied for the linearization and parametric representation of the dissolution curves. The surface morphology of the microcapsules was examined by using scanning electron microscopy. The results revealed that using a lower polymers blend concentration level, a higher drug loading and ethylene-vinylacetate copolymer as a coacervation-inducing agent resulted in the formation of fairly spherical microcapsules of high monodispersity and better surface characteristics and extended the drug release period (t: time at which 63.2 percent of the medicament dissolved = 6.052 h in simulated gastric fluid (S.G.F, pH 1.2) – 5.151 h in simulated intestinal fluid (S.I.F, pH 7.4). in contrast, polyisobutylene microcapsules prepared under the same experimental conditions were irregular, macroporous, and having the fastest release rate (t= 4.48 h (S.G.F, pH 1.2) – 2.051 h (S.I.F, pH 7.4)). Studies of the drug release thermodynamics by the Arrhenius equation demonstrated clearly that the release of allopurinol is an energy-linked process by a single release mechanism. The formulation of microcapsules prepared using ethylene-vinylacetate copolymer into tablets, prolonged greatly the drug release.

On the volume change on non covalent gels in solvent-non solvent mixtures

In this paper, the volume change on polysaccharide gels in non solvent mixtures is investigated. No phase transition is observed. A reversible decrease of the swelling volume is obtained directly related to the mechanical properties of the gels and to the charge parameters of the polymers. The effect of deswelling in presence of acetone or alcohol is increasing from agarose, k-carrageenan and i-carrageenan.

Analysis of nonsolvent–solvent–polymer phase diagrams and their relevance to membrane formation modeling

AbstractCalculations have been carried out, based on Flory–Huggins solution theory, to analyze the behavior of the ternary nonsolvent–solvent–polymer phase diagram for typical membrane‐forming systems. Consideration is given to the behavior of the spinodal as well as binodal curves, tie‐line slopes, and critical points as a function of various parameters, most especially those related to the concentration dependency of the interaction parameters. Implications regarding membrane structure formation are discussed, and the suitability of different functional forms for the interaction parameter concentration dependence is also analyzed.The net result of these calculations is to demonstrate the importance of the various parameters in controlling the phase‐diagram behavior and particularly to show the critical role of the concentration dependence of the solvent–polymer interaction parameter in affecting the nature of the miscibility gap.

Cellulose-walled microcapsules: 1. The effect of the solvent-non solvent proportions on the preparation of microcapsules from the system ethyl cellulose-chloroform-ethane diol.

The phase diagram of the system ethyl cellulose-chloroform-ethane diol has been studied and the differing phase regions determined. The effect of temperature of these regions is recorded. The phase diagram is used to determine the optimal conditions for the preparation of microcapsules with a phenobarbitone core and the size distribution of the microcapsules is recorded.

Dilute Solution Properties of Water-Soluble Incompletely Substituted Cellulose Acetate

Water-soluble incompletely substituted cellulose acetate (CA) was synthesized by the hydrolysis of cellulose diacetate with hydrochloric acid. CA having a degree of substitution DS between 0.39 and 0.81 was water-soluble. The CA (DS=0.49) whole polymer was fractionated into 15 parts, using water–methanol as the solvent–nonsolvent by the successive solution method. The CA(DS=0.49) polymer was soluble in highly polar organic solvents. Solution viscosity, light scattering, and membrane osmometry measurements were performed at 25°C on these fractions in N,N-dimethylacetamide (DMAc), dimethyl sulfoxide (DMSO), water, and formamide. The fractions had ratios of weight-to-number-average molecular weight Mn/Mn of approximately 1.3, independent of Mw. The following relations between limiting viscosity number [η], z-average radius of gyration ‹S2›z1/2 and Mw were obtained: [η]=0.19 Mw0.60 (cm3 g−1) and ‹S2›z1/2=0.50×10−8 Mw0.52 (cm) in DMAc at 25°C. Flory’s viscosity parameter Φ in DMAc was (1.82−2.18)×1023, showing a small molecular weight dependence. The short-range interaction parameter A was estimated thermodynamically as 1.33×10−8 (cm) in DMAc and the conformation parameter σ found to be 2.29. The effect of DS on the molecular characteristics of cellulose acetate is discussed.

Fractionnement de copolymeres poly(isobutylene)-poly(styrene) prepares par voie radiochimique: Comparaison entre l'elution fractionnee sur colonne avec gradient thermique et la precipitation fractionnee

Fractionation by the gradient elution method (EFGT) of radiation poly(styrene)-poly (isobutylene) copolymers has been performed. Conditions for best fractionation efficiency have been sought. The influences of copolymer weight to be fractionated, elution rate and column length have been examined. EFGT results have been compared with those obtained by fractional precipitation (PF). The two methods lead to the same results when the sensitivity to the chemical composition of the solvent-non solvent system is temperature independent (benzene-isopropanol). They lead to different results (EFGT fractionation is more sensitive to chemical composition than PF fractionation) when the sensitivity to chemical composition of the solvent-non solvent system decreases with rising temperature (cyclohexane-isopropanol). This difference results from the use of thermal gradient in EFGT (the top of the column is at a higher temperature than the bottom).