AB block copolymers of epsilon-caprolactone and (L)-lactide could be prepared by ring-opening polymerization in the melt at 110 degrees C using stannous octoate as a catalyst and ethanol as an initiator provided epsilon-caprolactone was polymerized first. Ethanol initiated the polymerization of epsilon-caprolactone producing a polymer with epsilon-caprolactone derived hydroxyl end groups which after addition of L-lactide in the second step of the polymerization initiated the ring-opening copolymerization of L-lactide. The number-average molecular weights of the poly(epsilon-caprolactone) blocks varied from 1.5 to 5.2 X 10(3), while those of the poly(L-lactide) blocks ranged from 17.4 to 49.7 X 10(3). The polydispersities of the block copolymers varied from 1.16 to 1.27. The number-average molecular weights of the polymers were controlled by the monomer/hydroxyl group ratio, and were independent on the monomer/stannous octoate ratio within the range of experimental conditions studied. When L-lactide was polymerized first, followed by copolymerization of epsilon-caprolactone, random copolymers were obtained. The formation of random copolymers was attributed to the occurrence of transesterification reactions. These side reactions were caused by the epsilon-caprolactone derived hydroxyl end groups generated during the copolymerization of epsilon-caprolactone with prepolymers of L-lactide. The polymerization proceeds through an eater alcoholysis reaction mechanism, in which the stannous octoate activated eater groups of the monomers react with hydroxyl groups. (C) 1997 John Wiley & Sons, Inc.

In general liquid-liquid demixing processes are responsible for the porous morphology of membranes obtained by immersion precipitation. For rapidly crystallizing polymers, solid-liquid demixing processes also generate porous morphologies. In this study, the interference of both phase transitions has been analyzed theoretically using the Flory-Huggins theory for ternary polymer solutions. It is demonstrated that four main thermodynamic and kinetic parameters are important for the structure formation in solution: the thermodynamic driving force for crystallization, the ratio of the molar volumes of the solvent and the nonsolvent, the polymer-solvent interaction parameter, and the rate of crystallization of the polymer compared to the rate of solvent-nonsolvent exchange. An analysis of the relevance of each of these parameters for the membrane morphology is presented. (C) 1997 John Wiley & Sons, Inc.

This review covers new experimental and theoretical physical research related to the formation of polymeric membranes by phase separation of a polymer solution, and to the morphology of these membranes. Two main phase separation processes for polymeric membrane formation are discussed: thermally induced phase separation and immersion precipitation. Special attention is paid to phase transitions like liquid-liquid demixing, crystallization, gelation, and vitrification, and their relation to membrane morphology. In addition, the mass transfer processes involved in immersion precipitation, and their influence on membrane morphology are discussed.

Membrane formation of polylactides has been studied using in situ analysis techniques. An experimental method based on the use of dark ground optics and reflected light illumination is used to monitor the mass transfer and phase separation dynamics during for mation. Additionally, the phase separation and structure formation has been studied using optical microscopy. The results of the dark ground optics technique for the polymer/solvent/nonsolvent systems poly-L-lactide/chloroform/methanol and poly-DL-lactide/chloroform/methanol showed that the diffusion kinetics were similar for the semicrystalline poly-L-lactide (PLLA) and the amorphous poly-DL-lactide. The influence of the molecular weight of the polymers on the diffusion kinetics was found to be negligible. Increasing the polymer concentration of the casting solution decreased the rate of diffusion. The phase separation of poly-DL-lactide was studied with optical microscopy and found to proceed via liquid-liquid demixing. For poly-L-lactide solutions of relatively low concentration (5-6% w/w), phase separation proceeded via liquid-liquid demixing followed by crystallization. For more concentrated PLLA solutions, phase separation proceeded directly via solid-liquid demixing processes. Additionally, for 6% w/w solutions of poly-L-lactide in dioxane immersed in methanol, precipitation also occurred solely via solid-liquid demixing.

The influence of liquid–liquid demixing, solid–liquid demixing, and vitrification on the membrane morphologies obtained from several polylactide-solvent-nonsolvent systems has been investigated. The polymers investigated were the semicrystalline poly-L-lactide (PLLA) and the amorphous poly-DL-lactide (PDLLA). The solvent-nonsolvent systems used were dioxane-water, N-methyl pyrrolidone-water and dioxane-methanol. For each of these systems it was attempted to relate the membrane morphology to the ternary phase diagram at 25°C. It was demonstrated that for the amorphous poly-DL-lactide the intersection of a glass transition and a liquid–liquid miscibility gap in the phase diagram was a prerequisite for the formation of stable membrane structures. For the semicrystalline PLLA a wide variety of morphologies could be obtained ranging from cellular to spherulitical structures. For membrane-forming combinations that show delayed demixing, trends expected on the basis of phase diagrams were in reasonable agreement with the observed membrane morphologies. Only for the rapidly precipitating system PLLA-N-methyl pyrrolidone-water were structures due to liquid–liquid demixing obtained when structures due to solid–liquid demixing were expected. Probably, rapid precipitation conditions promote solid–liquid demixing over liquid–liquid demixing, because the activation energy necessary for liquid–liquid demixing is lower than that for crystallization. © 1996 John Wiley & Sons, Inc.

The phase separation processes occurring in poly(L-lactide) (PLLA)-chloroform-methanol mixtures and poly(DL-lactide) (PDLLA)-chloroform-methanol mixtures have been studied using differential scanning calorimetry, cloud point measurements, and optical microscopy. It is demonstrated that liquid-liquid demixing occurs in ternary solutions of PDLLA at sufficiently high methanol concentrations. For PLLA-containing solutions, both liquid-liquid demixing processes and solid-liquid demixing processes occur. The most important parameters for the phase separation process are the applied cooling rate and the polymer concentration. Nonequilibrium phase separation processes play an important role in the phase separation of ternary PLLA solutions. Due to the high activation energy needed for crystallization, liquid-liquid demixing will usually precede solid-liquid demixing even if solid-liquid demixing is favored thermodynamically. Only at low cooling rates and high polymer concentration does solid-liquid demixing take place without the interference of liquid-liquid demixing.

Isothermal phase diagrams for the semicrystalline poly-L-lactide (PLLA) and the amorphous poly-DL-lactide (PDLLA) in combination with several solvent-nonsolvent combinations (dioxane/water, dioxane/methanol, chloroform/methanol, and NMP/water) have been determined. The locations of the liquid-liquid miscibility gap, the solid-liquid miscibility gap and the vitrification boundary in the isothermal phase diagrams at 25 degrees C were identified. The liquid-liquid miscibility gap for the systems with PLLA was located in the same composition range as the corresponding systems with PDLLA. For the systems containing PLLA solid-liquid demixing was thermodynamically preferred over liquid-liquid demixing. Attempts were made to correlate the experimental findings with predictions on the basis of the Flory-Huggins theory for ternary solutions using interaction parameters derived from independent experiments. Qualitative agreement was found between the theoretical predictions and the experimentally obtained liquid-liquid miscibility gap. No good agreement was found for the solid-liquid miscibility gap. (C) 1996 John Wiley & Sons, Inc.

The influence of solid-liquid demixing, liquid-liquid demixing and vitrification on the morphology of polylactide membranes has been investigated. To study the effects of crystallization of polylactides on the membrane and morphology, polylactides of varying stereoregularity were used. The polymers applied were poly-l-lactide (PLLA) and copolymers with different molar ratios of l-lactide and d-lactide [poly-L95/D5-lactide (PLA95), poly-L80/D20-lactide (PLA80) and poly-L50/D50-lactide (PDLLA)]. Solutions of polylactides in chloroform cast on a glass plate were immersed in methanol. From solutions containing the slowly crystallizing PLA80 or uncrystallizable PDLLA porous membranes were obtained if the phase separated system was removed from the nonsolvent bath within a few hours after immersion. After longer equilibration times in methanol the structure collapsed. The swelling in the nonsolvent methanol was too high to allow stabilization of the liquid-liquid demixed structure by vitrification. Stable membranes were easily obtained with more rapidly crystallizing polymers like PLLA. Casting solutions with low PLLA concentrations gave membranes with a cellular morphology due to liquid-liquid demixing by nucleation and growth of a polymer poor phase. Crystallization only played a role in the fixation of the liquid-liquid demixed structure. At increasing PLLA concentrations the demixing sequence gradually reversed to crystallization followed by liquid-liquid demixing. In these cases membranes with porous spherulites or spherulites surrounded with a cellular layer were obtained.

Highly crystalline porous hollow poly (L-lactide) (PLLA) fibres suitable for the delivery of various drugs were obtained using a dry-wet spinning process. The pore structure of the fibres could be regulated by changing the spinning systems and spinning conditions. Using the spinning system PLLA-dioxane-water, fibres with a dense toplayer and a spongy sublayer were obtained. The spinning system PLLA-chloroform/toluene-methanol yielded fibres with a very open porous structure. The membrane formation of the former system probably occurs by liquid-liquid demixing followed by crystallization of the polymer rich phase. In the membrane formation process of the spinning system, PLLA-chloroform/toluene-methanol crystallization probably plays a dominant role. The membrane formation process will be related to basic principles of phase separation. The fibres are suitable for the long term zero order delivery of the contraceptive 3-ketodesogestrel and the short term zero order delivery of the cytostatic agent, cisplatin. The drugs are released by dissolution of the drug crystals in the fibre core followed by diffusion through the membrane structure. Short term release of adriamycin could be obtained through an adsorption-desorption mechanism. The pore structures of the fibres have a large influence on the release rates of the drugs investigated. When fibres with dense toplayers were used. low release rates of drugs were observed whereas fibres with well interconnected pore structures over the fibre wall showed very high release rates.