Hydrolytic Degradation Studies Research Articles

Hydrolytic degradation and diffusion studies on a polyphosphate ester

AbstractA polyphosphate ester was synthesized by interfacial polycondensation of bisphenol‐A and phenylphosphorodichloridate. Accelerated hydrolytic degradation studies were conducted under alkaline conditions. The effect of concentration of alkali and temperature were monitored. The rate of degradation reached a maximum value at 6 molar sodium hydroxide solution and then reduced. The activation energy for hydrolytic degradation was found to be 45 kcal/mol. Diffusion of alkali into the polymer pellet was studied at various concentrations of alkali and at various temperatures. The rate of diffusion also attained a maximum at 6M NaOH and the activation energy for diffusion process was found to be 12 kcal/mol. © 2002 John Wiley & Sons, Inc. J Appl Polym Sci 84: 701–708, 2002; DOI 10.1002/app.10008

Hydrolytic degradation of nitrendipine and nisoldipine

The development of a new HPLC-UV diode array procedure applied to follow the hydrolytic degradation of two well-known 4-nitrophenyl-1,4-dihydropyridine derivatives, nitrendipine and nisoldipine is reported. Hydrolysis of each drug were carried out in ethanol/Britton–Robinson buffer at different pHs, stored into amber vials at controlled temperatures of 40, 60 and 80 °C and periodically sampled and assayed by HPLC. Nitrendipine degradation in different parenteral solutions was also evaluated. The HPLC procedure exhibited an adequate selectivity, repeatability (<1%) and reproducibility (<2%). The recoveries were higher than 98% with CV of 1.13 and 1.54% for nitrendipine and nisoldipine, respectively. A significant degradation was observed at alkaline pH (>pH 8) with a first order kinetic for both drugs. At pH 12, 80 °C, k values of 3.56×10 −2 h −1 and 2.22×10 −2 for nitrendipine and nisoldipine, respectively were obtained. Also, activation energies of 16.8 and 14.7 kcal mol −1 for nitrendipine and nisoldipine, respectively, were calculated. Furthermore, from the results obtained from hydrolytic degradation in different solutions for parenteral use, we can affirm that solutions significantly increased the degradation of nitrendipine. In conclusion, the HPLC proposed procedure exhibited adequate analytical requirements to be applied to the hydrolytic degradation studies of nitrendipine and nisoldipine. Furthermore, all tested parenteral solutions significantly increased the hydrolytic degradation of nitrendipine, the composition of solution being a relevant factor.

Hydrolytic and enzymatic degradation of copoly(ester amide)s based on l-tartaric and succinic acids

The hydrolytic and enzymatic degradation of a series of crystalline copoly(ester amide)s derived from l-tartaric and succinic acids, 1,6 hexanediamine and 1,6-hexanediol with ester/amide groups ratios 3/97, 10/90, 15/85 and 20/80 was investigated. The hydrolytic degradation study was carried out at 37°C in buffered solution at pH 7.4. Changes taking place in sample weight, molecular weight, chemical constitution and thermal properties of the polymer were evaluated. Degradation proceeded with a notable increment in crystallinity and entailing slight but significant changes in the T g and T m temperatures. It was found that copoly(ester amide)s degraded faster than the parent poly(hexamethylene-di- O-methyl- l-tartaramide) and that the rate of degradation increased with the content in ester groups. It was also showed that degradation is accompanied by formation of cyclic succinimide units indicative of a scission mechanism based on the occurrence of intramolecular imidation reactions. The enzymatic degradation of these copoly(ester amide)s with papain was comparatively examined for a preliminary evaluation of their potential biodegradability.

Geminal poly(silyl ester)s: Highly labile degradable polymers

Geminal silyl ester linkages were used for the backbone construction of linear polymers, which exhibit rapid cleavage in the presence of atmospheric water. A series of poly(gem-silyl ester)s with two ester groups flanking each silicon atom were synthesized, in order to probe the effects of different silyl-substituted side-chain groups upon the physical and chemical properties. The transsilylation condensation reaction of bis(trimethylsilyl) terephthalate with dichlorodiisopropylsilane, dichlorodicyclohexylsilane, dichloromethyl-n-octadecylsilane, and dichloromethyl-4-methylphenethylsilane gave the four poly(gem-silyl ester)s with two isopropyl, two cyclohexyl, one methyl plus one octadecyl, and one methyl plus one 4-methyl-phenethyl side-chain groups per silicon, respectively. The polymers were characterized by NMR (1H, 13C, and 29Si), infrared spectroscopy (IR), size-exclusion chromatography (SEC), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Hydrolytic degradation studies of the polymers solvated in tetrahydrofuran and as bulk samples in the solid state were performed in the presence of atmospheric water as the nucleophilic cleavage agent, and the molecular weight loss was monitored by SEC. Poly(diisopropylsilyl terephthalate) (1a) and poly(dicyclohexylsilyl terephthalate) (1b) were found to be more stable towards nucleophilic degradation in comparison to poly(methyl-n-octadecylsilyl terephthalate) (1c) and poly(methyl-4-methylphenethylsilyl terephthalate) (1d), due to the presence of sterically bulky isopropyl or cyclohexyl groups attached to the silicon atoms. All of the polymers degraded into small molecules upon hydrolysis, with the exception that the degradation products of 1c and 1d self-condensed in the solid state to form the respective polysiloxanes. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3606–3613, 1999

Geminal poly(silyl ester)s: Highly labile degradable polymers

Geminal silyl ester linkages were used for the backbone construction of linear polymers, which exhibit rapid cleavage in the presence of atmospheric water. A series of poly(gem-silyl ester)s with two ester groups flanking each silicon atom were synthesized, in order to probe the effects of different silyl-substituted side-chain groups upon the physical and chemical properties. The transsilylation condensation reaction of bis(trimethylsilyl) terephthalate with dichlorodiisopropylsilane, dichlorodicyclohexylsilane, dichloromethyl-n-octadecylsilane, and dichloromethyl-4-methylphenethylsilane gave the four poly(gem-silyl ester)s with two isopropyl, two cyclohexyl, one methyl plus one octadecyl, and one methyl plus one 4-methyl-phenethyl side-chain groups per silicon, respectively. The polymers were characterized by NMR (1H, 13C, and 29Si), infrared spectroscopy (IR), size-exclusion chromatography (SEC), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Hydrolytic degradation studies of the polymers solvated in tetrahydrofuran and as bulk samples in the solid state were performed in the presence of atmospheric water as the nucleophilic cleavage agent, and the molecular weight loss was monitored by SEC. Poly(diisopropylsilyl terephthalate) (1a) and poly(dicyclohexylsilyl terephthalate) (1b) were found to be more stable towards nucleophilic degradation in comparison to poly(methyl-n-octadecylsilyl terephthalate) (1c) and poly(methyl-4-methylphenethylsilyl terephthalate) (1d), due to the presence of sterically bulky isopropyl or cyclohexyl groups attached to the silicon atoms. All of the polymers degraded into small molecules upon hydrolysis, with the exception that the degradation products of 1c and 1d self-condensed in the solid state to form the respective polysiloxanes. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3606–3613, 1999

Hydrolytic degradation of peroxide modified poly(L-lactide)

Poly(L-lactide) (PLLA) was prepared by a tin(II)-octanoate initiated ring-opening polymerization in the melt and separately melt modified with tert-butylperoxy benzoate (0.1, 0.25 and 0.5 wt%) in order to deactivate the residual tin compounds and reduce melt degradation. Injection molded specimens of unmodified and peroxide-modified PLLA were prepared for a hydrolytic degradation study, where the changes in the weight, mechanical strength, molar mass and morphology were studied during the immersion in buffer solutions (pH 7.4) at 37 °C. The hydrolytic degradation of both the unmodified and the peroxide-modified PLLA was rapid. This was found to depend on the residual dilactide content, which in all samples was above 11% before the immersion. The peroxide modified samples underwent a more rapid hydrolytic degradation than the unmodified ones, which can be related to the morphological changes caused by the peroxide modification.

Synthesis of novel hydrolytically degradable hydrogels for controlled drug release

This paper describes synthesis of hydrolytically degradable gels based on N-(2-hydroxypropyl)-methacrylamide copolymers with high potential for use in the synthesis of new drug release systems. The first part deals with a study of the dependence between conditions of crosslinking copolymerization, the course of copolymerization and final properties of hydrogels thus formed. The second part is devoted to the study of hydrolytic degradation of hydrogels and in vitro studies of doxorubicin and polymer-doxorubicin conjugate release from hydrogel matrix. We have shown that the hydrogels under study were stable under acidic conditions (in buffers at pH 5 and lower) and hydrolytically degradable at physiological pH (7.4). Both drug forms, free doxorubicin and its conjugate with water-soluble polymeric drug carrier, can be released from the hydrogel matrix at a rate depending on the rate of drug diffusion from the hydrogel, or the rate of hydrogel degradation, or at a rate controlled by a combination of both processes. In all cases the hydrogel matrix was degraded and a hydrophilic water-soluble polymeric product was formed. Biological evaluation of drug-hydrogel systems described in this paper is under way.

Degradable polyurethane networks based on d,l-lactide, glycolide, ε-caprolactone, and trimethylene carbonate homopolyester and copolyester triols

Several trifunctional, hydroxy-telechelic polyester and poly(ester-carbonate) homopolymers and copolymers were synthesized by the triol-initiated, ring-opening bulk polymerization of d,l-lactide, glycolide, ε-caprolactone, and/or trimethylene carbonate. The molar compositions of the copolymers were determined from 13C n.m.r. spectra; hydroxy equivalent weights were determined by acetylation titration, and the glass transition temperatures ( T g) and melting points were determined by differential scanning calorimetry (d.s.c.). Crosslinked polyurethane networks were prepared by reacting the hydroxy-telechelic prepolymers with tolylene diisocyanate. Network characterization included determination of sol content by solvent extraction, T g by d.s.c., tensile properties by stress-strain measurements, and degradation properties by hydrolytic degradation studies. Equilibrium swelling results indicated that the per cent weight gains correlated well with the prepolymer hydroxy equivalent weights, with the exception of the poly(glycolide- co-trimethylene carbonate) network. The poly( d,l-lactide) and poly( d,l-lactide- co-trimethylene carbonate) (PLTMC) networks had the highest tensile strengths of 49.60 and 41.27 MPa, respectively, and glass transition temperatures of 51.3 and 21.3°C, respectively. All other networks were highly flexible with tensile strengths of 12 MPa or less. Hydrolytic degradation studies were conducted by placing network samples in a solution of phosphate-buffered saline (pH = 7.4) at 37°C. Weight uptake of buffer and weight loss of the networks were monitored gravimetrically over time. Tensile properties, monitored as a function of degradation time, indicated that the poly(ε-caprolactone- co- d,l-lactide) and PLTMC networks displayed a linear loss of strength with respect to weight during the first 30 days of degradation; the other networks degraded either too slowly or too quickly to establish such a linear relationship.

Hydrolytic degradation and morphologic study of poly-p-dioxanone.

The in vitro hydrolytic degradation of 2-0 size PDS monofilament suture was studied for the purpose of revealing its morphologic structure and degradation mechanism. The sutures were immersed in phosphate buffer of pH 7.44 for up to 120 days at 37 degrees C. These hydrolyzed sutures were examined by the changes in tensile properties, weight, thermal properties, x-ray diffraction structure, surface morphology, and dye diffusion phenomena. It was found that hydrolysis had significant effects on the change of PDS fiber morphology and properties. Hydrolysis, however, had no significant effect on overall molecular orientation of the fiber until the very late stage. PDS suture fibers retained their skeleton throughout the earlier periods of hydrolysis concurrent with mass and tensile strength losses. PDS sutures exhibited an absorption delay of 120 days. Both heat of fusion and melting point exhibited a maximum function of hydrolysis time. Hydrolysis of PDS suture fibers proceeded through two stages: random scission of chain segments located in the amorphous regions of microfibrils and intermicrofibrillar space, followed by stepwise scission of chain segments located in the crystalline regions of microfibrils. Dye diffusion data showed that the passage along the longitudinal direction of the fiber was relatively easier than the lateral direction as evident in the diffusion coefficient, activation energy, and flexibility of chain segments. Swiss-cheese model of fiber structure appears to describe the observed dye diffusion phenomena and their dependence on hydrolysis time and dying temperature.

Bioabsorbable composites. I: Fundamental design considerations using free radically crosslinkable matrices

AbstractBioabsorbable composites have been fabricated, consisting of poly (glycolic acid) surgical mesh embedded in free radically crosslinked poly (D, Iactide‐co‐8‐caprolactone) fumarate‐ or poly(D, Iactide‐co‐‐glycolic acid) fumarate‐based matrices. Styrene and methyl methacrlate were investigated as hydrophobic comonomers and were found to significantly improve the degree of crosslinking, tensile strength and retention of physical properties during the initial stages of degradation particularly styrene. Hydrolytic degradation studies showed that the neat poly(D, L‐lactide‐co‐8caprolactone) fumarate matrix dwas excessively hydrophilic, failing after 10 days of immersion; a matrix modified with 25 wt% styrene underwent a steady, nearly linear loss in mass over a period of 35 days without fragmentation. A composite based on neat poly (D, L‐lactide‐co‐8‐caprolactone) fumarate displayed a tensile strength of 37 Mpa and modulus of 107 Mpa; addition of 25 wt% styrene yielded tensile strength and modulus of 64 Mpa and 689 Mpa, respectively. A silane coupling agent was shown to dramatically improve the fiber‐matrix interfacial adhesion; tensile strength of a poly(D, L‐lactide‐co‐glycolic acid) fumarate compsite was increase from 84 to 92 MPa upon fiber pretreatment. Improved adhesion was also demonstrated using SEM. Bioabsorbable composites are rigid at biological temperatures, but some can be custom formed at elevated temperatures, which might be useful in certain surgical applications.

Polymers for biodegradable medical devices: II. Hydroxybutyrate-hydroxyvalerate copolymers: hydrolytic degradation studies

The hydrolytic degradation of poly(hydroxybutyrate) together with a series of hydroxybutyrate-hydroxy-valerate copolymers has been studied. The effects of copolymer composition and molecular weight are presented together with the results of varying pH and temperature on the degradation rate. Degradation has been monitored by weight loss and water uptake measurements together with goniophotometric, surface energy and scanning electron microscopic studies. Some comparisons with the more widely used so-called ‘biodegradable’ polymers, poly(glycolic acid), poly(dioxanone) and the glycolic-lactic acid (90:10) copolymers are presented together with the effect of blood plasma on the degradation process.

Study of hydrolytic degradation of polyester plasticizers by NMR 1H and 13C methods

Methods were developed for the study of kinetics of hydrolysis of polyester plasticizers with alkoxyl and acyl end groups using the NMR 1H and 13C techniques. It was shown that, independent of the type and size of end group, the neopentyl glycol-acid bond is more resistant to hydrolysis than the ethylene glycol-acid bond. It was also found that the hydrolytic stability of ester bonds which are formed in polyester by a monofunctional reagent decreases with a reduction in the hydrocarbon chain length of this reagent. With fairly long chain end groups the hydrolytic stability of polyester plasticizers is determined by the stability of dicarboxylic acid-glycol bonds.

Hydrolytic and thermal degradation study of some model and polymeric siloxane compounds

It was found during study of the thermal degradation of polysiloxanes that much of this process consists of depolymerization involving the hydroxyl end groups [1–4]. We were able to show that fracture of the SiC bond accompanied by methane formation plays an important part in the degradation, because it leads to decay of the terminal OH groups [4]. In the case of polydimethylsiloxane, the rate of SiO bond fracture is about 3 orders larger than that of SiC bonds [5]; this is due to the considerable resistance of the SiCH 3 bond to nucleophilic attack. The partial replacement of methyl groups surrounding the Si by groups less resistant to hydrolytic cleavage of the SiC bond can be expected to reduce the thermal degradation rate due to the more rapid consumption of the terminal OH groups of the polymer molecules. Quite a lot of information is given in the literature about the chemical resistance of the SiC bond of different silanes. This was found to depend on the radical structure, the nature of other radicals connected to the Si, and the types of reagent used. Unsaturated alkyl groups in tetraalkylsilanes are not detached by the action of nucleophilic reagents, but the methyl group of even tetramethylsilane is fractured during electrophilic attack by the sulphuric acid proton [6]. The introduction of electronegative atoms into the alkyl group will reduce the stability of the SiC bond [7], and sometimes also weaken the resistance of the adjacent SiCH 3 bonds to nucleo- and electrophilic attack [8]. The SiC 6H 5 bond of silanes fractures under nucleo- or electrophilic action: the aryl group dissociates more easily than the alkyl group [9]. The introduction of a very strong electron-donating group in the para-position with respect to the Si atom will increase the rate of fracture of the SiC 6H 4X bond during electrophilic attack: the p-CH 3OC 6H 4Si bond will be fractured about 10 3 times faster than the SiC 6H 5 bond[10, 11].

The acid hydrolyses of poly-oxymethylene diisopropyl ethers

A homologous series of polyoxymethylene di-isopropyl ethers [RO(CH2O)nR] from n = 1 through n = 6 has been prepared and characterized by gas/liquid partition chromatography, infrared spectroscopy, and other techniques. The acid hydrolyses of the series indicated no rate dependence on chain length between the endgroups, which suggests that the rate of hydrolysis is not dependent on the remaining intermediate group. The rate constants and activation energy are reported, as well as those from the literature. The conclusion is reached that hydrolytic degradation studies of formaldehyde-crosslinked cellulose cannot yield information on the chain lengths of the crosslinks.

Evidence for the structure of brain triphosphoinositide from hydrolytic degradation studies.

Evidence for the structure of brain triphosphoinositide from hydrolytic degradation studies.