Polycaprolactone preparation

Copolymers of S-caprolactone and L-lactide are elastomeric when prepared from 25% S-caprolactone and 75% L-lactide, and rigid when prepared from 10% S-caprolactone and 90% L-lactide (47). Blends of poly-DL-lactide and polycaprolactone polymers are another way to achieve unique elastomeric properties. Copolymers of S-caprolactone and glycoHde have been evaluated in fiber form as potential absorbable sutures. Strong, flexible monofilaments have been produced which maintain 11—37% of initial tensile strength after two weeks in vivo (48). 

Commercial end functional polymers have been converted to alkoxyamincs and used to prepare PKO-Worri-PS.040 The hydroxyl group of alkoxyamine 284 was used to initiate ring-opening polymerization of caprolactonc catalyzed by aluminum tris(isopropoxide) and the product subsequently was used to initiate S polymerization by NMP thus forming polycaprolactone-Wodr- P8.641 The alternate strategy of forming PS by NMP and using the hydroxyl chain end of the product to initiate polymerization of caprolactonc was also used. 

Surfactants are prepared which contain carboxylic acid ester or amide chains and terminal acid groups selected from phosphoric acid, carboxymethyl, sulfuric acid, sulfonic acid, and phosphonic acid. These surfactants can be obtained by reaction of phosphoric acid or phosphorus pentoxide with polyhydroxystearic acid or polycaprolactone at 180-190°C under an inert gas. They are useful as polymerization catalysts and as dispersing agents for fuel, diesel, and paraffin oils [69]. 

Preparation and characteristics of ABA type polycaprolactone-b-polydimethyl-siloxane block copolymers have been recently reported 289). In this study, ring-opening polymerization of e-caprolactone was achieved in melt, using a hydroxybutyl terminated PSX as the initiator and a catalytic amount of stannous octoate. Reactions were completed in two steps as shown in Reaction Scheme XIX. 

Aliphatic polyesters based on monomers other than a-hydroxyalkanoic acids have also been developed and evaluated as drug delivery matrices. These include the polyhydroxybutyrate and polyhydroxy valerate homo- and copolymers developed by Imperial Chemical Industries (ICI) from a fermentation process and the polycaprolactones extensively studied by Pitt and Schindler (14,15). The homopolymers in these series of aliphatic polyesters are hydrophobic and crystalline in structure. Because of these properties, these polyesters normally have long degradation times in vivo of 1-2 years. However, the use of copolymers and in the case of polycaprolactone even polymer blends have led to materials with useful degradation times as a result of changes in the crystallinity and hydrophobicity of these polymers. An even larger family of polymers based upon hydroxyaliphatic acids has recently been prepared by bacteria fermentation processes, and it is anticipated that some of these materials may be evaluated for drug delivery as soon as they become commercially available. 

The neutral fats used in the preparation of the hydrophobic core of the several liposphere-vaccine formulations described here included tricaprin and tristearin, stearic acid, and ethyl stearate. The phospholipids used to form the surrounding layer of lipospheres were egg phosphatidylcholine and dimyristoyl phosphatidylg-lycerol. Polymeric biodegradable lipospheres were prepared from low molecular weight polylactide (PLA) and polycaprolactone-diol (PCL). 

Liposphere formulations are prepared by solvent or melt processes. In the melt method, the active agent is dissolved or dispersed in the melted solid carrier (i.e., tristearin or polycaprolactone) and a hot buffer solution is added at once, along with the phospholipid powder. The hot mixture is homogenized for about 2 to 5 min, using a homogenizer or ultrasound probe, after which a uniform emulsion is obtained. The milky formulation is then rapidly cooled down to about 20°C by immersing the formulation flask in a dry ice-acetone bath, while homogenization is continued to yield a uniform dispersion of lipospheres. 

All liposphere formulations prepared remained stable during the 3-month period of the study, and no phase separation or appearance of aggregates were observed. The difference between polymeric lipospheres and the standard liposphere formulations is the composition of the internal core of the particles. Standard lipospheres, such as those previously described, consist of a solid hydrophobic fat core composed of neutral fats like tristearin, whereas, in the polymeric lipospheres, biodegradable polymers such as polylactide or polycaprolactone were substituted for the triglycerides. Both types of lipospheres are thought to be stabilized by one layer of phospholipid molecules embedded in their surface. 

Crosslinked poly(urea-urethane)s consisting of tris(4-isocyanatophenyl)-methane, trimethylolethane, and 4,4 -methylenebis(3-chloro-2,6-diethyl-aniline) were prepared by Rukavina et al. (2) and used in optical lenses. Polycaprolactone diol derivatives were also prepared by Rukavina et aL (3) and used in optical lenses. 

Poly(urethane urea)polysulfide resins consisting of polycaprolactone diol, 4,4 -methylenebis(cyclohexyl isocyanate), and bis-epithiopropyl sulfide, were prepared by Bojkova et al. (4) and used as optical lenses having good refractive index and good impact resistance/strength. 

Figure 2 Foam prepared from liquefied wood in the presence of polycaprolactone.

The IPNs prepared were composed of a rubbery polyurethane and a glassy epoxy component. For the polyurethane portion, a carbodiimide-modified diphenyl-methane diisocyanate (Isonate 143L) was used with a polycaprolactone glycol (TONE polyol 0230) and a dibutyltin dilaurate catalyst (T-12). For the epoxy, a bisphenol-A epichlorohydrin (DER 330) was used with a Lewis acid catalyst system (BF -etherate). The catalysts crosslink via a ring-opening mechanism and were intentionally selected to provide minimum grafting with any of the polyurethane components. The urethane/epoxy ratio was maintained constant at 50/50. A number of fillers were included in the IPN formulations. The materials used are shown in Table I. 

Until recently, hot-melt extrusion had not received much attention in the pharmaceutical literature. Pellets comprising cellulose acetate phthalate were prepared using a rudimentary ram extruder in 1969 and studied for dissolution rates in relation to pellet geometry. More recently, production of matrices based on polyethylene and polycaprolactone were investigated using extruders of laboratory scale. Mank et al. reported in 1989 and 1990 on the extrusion of a number of thermoplastic polymers to produce sustained release pellets.A melt-extrusion process for manufacturing matrix drug delivery systems was reported by Sprockel and coworkers.As one can see, a review of the pharmaceutical scientific literature does not elucidate many applications for hot-melt extrusion in this field. 

Lee H, Yoon H, Kim G (2009) Highly oriented electrospun polycaprolactone micro/ nanoflbers prepared by a field-controllable electrode and rotating collector. Appl Phys A Mater Sci Process 97(3) 559—565... 

The extruder can be used for a variety of polymerizations even if no preformed polymer is present.89 These include the continuous anionic polymerization of caprolactam to produce nylon 6,90 anionic polymerization of capro-lactone 91 anionic polymerization of styrene 92 cationic copolymerization of 1,3-dioxolane and methylal 93 free radical polymerization of methyl methacrylate 94 addition of ammonia to maleic anhydride to form poly(succin-imide) 95 and preparation of an acrylated polyurethane from polycaprolactone, 4,4 -methylenebis(phenyl isocyanate), and 2-hydroxyethyl acrylate.96 The technique of reaction injection molding to prepare molded parts is slightly different. Polyurethanes can be made this way by... 

Preparation of Cast Elastomers. The cast elastomers were prepared in a two-step procedure. First prepolymers were made from one polyether polyol (poly(oxy-tetramethylene) glycol of 1000 M.W., (POTMG)) and two polyester polyols (adipate polyester of 2000 M.W. (PAG) and polycaprolactone of 1250 M.W. (PCL)) by reaction with the corresponding diisocyanates (MDI, PPDI, CHDI or NDI) at an NCO/OH ratio of 2/1. The temperature was maintained at 80°C and periodic samples were withdrawn to determined the isocyanate content. When the isocyanate content of the mixture reached within 0.3% of the calculated value, the reaction was stopped by cooling. The prepolymer could be kept for a period of six months in the absence of moisture. The isocyanate-terminated prepolymers were then chain-extended with... 

Polycaprolactone synthesis was performed in two scales preparative, and screening scale. In preparative scale, synthesis was performed in a three-neck flask with an overhead mechanical stirrer and a temperature controller in presence of an anhydrous solvent. Toluene was selected as the best solvent for PCL synthesis [24], In screening scale, synthesis was performed in smaller scale inside glass vials in a J-Kem parallel synthesizer with either 6-vial or 12-vial reactor. 

Smith et al. (179) described the preparation of a hard and adherent coating by irradiation of an unsaturated polyurethane-polycaprolactone resin. 

Liu L, Wang YS et al (2005) Preparation of chitosan-g-polycaprolactone copolymers through ring-opening polymerization of epsilon-caprolactone onto phthaloyl-protected chitosan. Biopolymers 78 163-170... 

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