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PubMed1999

Qualitative determination of polyvinylpyrrolidone type by near-infrared spectrometry.

Soluble polyvinylpyrrolidones are very useful and versatile pharmaceutical auxiliaries. The different types of povidone are characterised by their viscosity measured in water, expressed as a K-value. We have developed a rapid, accurate, reliable, and non-destructive near infrared (NIR) spectroscopy method for the determination of PVP type and consequently identification thereof. We have implemented chemometrics onto NIR spectra collected in diffuse reflectance mode using fibre optics to build a qualitative model that enables us to obtain useful analytical information. A principal component analysis and a modelling technique soft independent modelling of class analogy (SIMCA) were applied. An approach to validate the method was developed.

Chemistry Techniques, Analytical↗
PubMed1999

Properties of solid dispersions of piroxicam in polyvinylpyrrolidone.

Solid dispersions of piroxicam were prepared with polyvinylpyrrolidone (PVP) K-17 PF and PVP K-90 by solvent method. The physical state and drug:PVP interaction of solid dispersions and physical mixtures were characterized by X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). FTIR analysis demonstrated the presence of intermolecular hydrogen bonding between piroxicam and PVP in solid dispersions. These interactions reflected the changes in crystalline structures of piroxicam. The amorphousness within the PVP moeity might be predicted in piroxicam dispersions by the disappearance of N-H or O-H peak of piroxicam. Dissolution studies indicated a significant increase in dissolution of piroxicam when dispersed in PVP. The better results were obtained with the lower molecular weight PVP K-17 than with higher molecular weight PVP K-90. The non-amorphous solid dispersions in PVP K-17 showed almost equally fast dissolution rates to amorphous dispersions in PVP K-90. The mechanism of dissolution of solid dispersion in PVP K-90 is predominantly diffusion-controlled due to the very high viscosity of PVP K-90. Dissolution was maximum with the amorphous solid dispersions containing drug:PVP K-17 1:5 and 1:6 which showed a 40-fold increase in dissolution in 5 min as compared with pure drug.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Interpolymer complexation. I. Preparation and characterization of a polyvinyl acetate phthalate-polyvinylpyrrolidone (PVAP-PVP) complex.

Polyvinyl acetate phthalate (PVAP) and polyvinylpyrrolidone (PVP) readily reacted in ethanol and acidic aqueous solutions to produce an insoluble PVAP-PVP complex. The complex has a pK(a) of 3.8. It is practically insoluble in common organic solvents, but dissolves in dimethylsulfoxide, an alkali or ammonical solution, and a 4:1 (v/v) mixture of methylene chloride and methanol. The powder X-ray diffraction analysis revealed the complex to be an amorphous material. The Fourier-transform infrared spectrum of the complex exhibited characteristics carbonyl stretching vibrations at 1724 and 1657 cm(-1) due to phthalate and acetate moieties in PVAP and cyclic amide groups in PVP, respectively, and at 1632 cm(-1) (appeared as a shoulder) due to cyclic amide groups of PVP bound to PVAP. The proton and carbon-13 (solution and solid-state) nuclear magnetic resonance spectra of the complex showed peak profiles that were linear combinations of those of PVAP and PVP. No new peaks appeared and no change in chemical shifts was observed due to complexation. The spectral data suggest that the interaction between PVAP and PVP probably initially involves the formation of hydrogen bonds between carbonyl groups of PVP and carboxylic groups of PVAP at some point of the polymer chains, causing the hydrophilic parts of the two flexible polymer chains strongly hydrophobic. As a result, the two polymer chains coil up into a compact structure and, consequently, precipitate out from the solution as an insoluble complex.

Chemistry, Pharmaceutical↗
PubMed2001

The influence of polyvinylpyrrolidone on naproxen complexation with hydroxypropyl-beta-cyclodextrin.

The combined effect of hydroxypropyl-beta-cyclodextrin (HPbetaCD) and polyvinylpyrrolidone (PVP) on the solubility of naproxen (NAP) was studied. Phase-solubility analysis at different temperatures was used to investigate interactions in aqueous solution between NAP and the carriers, either alone or in combination. Equimolar NAP-HPbetaCD solid systems, in the presence or the absence of 15% (w/w) PVP, were prepared by cogrinding, kneading, coevaporation or freeze-drying, and characterized by differential scanning calorimetry, X-ray powder diffraction analysis, infrared spectroscopy and dissolution rates. The combined use of PVP and HPbetaCD resulted in a synergistic increasing effect of the aqueous solubility of NAP (120 times that of the pure drug). The phenomenon was interpreted in terms of the strongest complexation capacity of HPbetaCD towards NAP, which was reflected by an about 65% increase in the apparent stability constant of the NAP-HPbetaCD complex in the presence of only 0.1% (w/v) PVP. Variations in thermodynamic parameters accounted for a PVP role in the formation of a NAP-HPbetaCD-PVP ternary complex. The positive effect of PVP also reflected on NAP dissolution rates from solid preparations, because all ternary systems, with the exception of physical mixtures, dissolved faster than the corresponding NAP-HPbetaCD binary systems. The results of solid state studies accounted for the occurrence of mechanically- and/or thermally-induced stronger interactions in ternary than in binary systems, that in some cases led to a complete loss of NAP crystallinity.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2004

Comparison of the effect of chitosan and polyvinylpyrrolidone on dissolution properties and analgesic effect of naproxen.

The solubilizing and absorption enhancer properties towards naproxen of chitosan and polyvinylpyrrolidone (PVP) have been investigated. Solid binary systems prepared at various drug-polymer ratios by mixing, cogrinding or kneading, were characterized by differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, and scanning electron microscopy, and tested for dissolution behavior. Both carriers improved drug dissolution and their performance depended on the drug-polymer ratio and the system preparation method. Chitosan was more effective than PVP, despite the greater amorphizing power of PVP as revealed by solid state analyses. The 3/7 (w/w) drug-carrier coground systems with chitosan and PVP were the best products enabling, respectively, an improvement of 4.8 and 3.6 times of drug dissolution efficiency. In vivo experiments in mice demonstrated that administration of 45 mg/kg of drug coground with PVP or chitosan resulted, respectively, in a 25 and 60% reduction of acetic acid-induced writhings in comparison to pure drug, which, instead, was statistically ineffective as compared to the control group. Moreover, the 3/7 (w/w) drug-chitosan coground product demonstrated an antiwrithing potency 2.4 times higher than the coground with PVP. Thus, the direct-compression properties and antiulcerogenic activity, combined with the demonstrated solubilizing power and analgesic effect enhancer ability towards the drug, make chitosan particularly suitable for developing a reduced-dose fast-release solid oral dosage form of naproxen.

Acetic Acid↗
PubMed2004

Aminoxyl radicals as crosslinks for macromolecules of polyvinylpyrrolidone.

Using polyvinylpyrrolidone as an example, it has been shown that photolysis of ceric ammonium nitrate at room temperature can result in crosslinking of macromolecules. This process correlates with the formation of stable aminoxyl radicals, which are registered by EPR. The mechanism involves photodissociation of nitrate radicals produced in the primary reaction into nitric oxide or nitrogen dioxide depending on the wavelength of the light, and simultaneous formation of macroradicals. The accumulation of aminoxyl radicals occurs owing to the acceptance of macroradicals by nitroso or nitro groups according to which mechanism of the nitrate radical photodissociation prevails. Similar radical reactions are observed in N-methyl-2-pyrrolidone.

Journal Article↗
PubMed2006

The potential application of chlorin e6-polyvinylpyrrolidone formulation in photodynamic therapy.

Much research has been focused on developing effective drug delivery systems for the preparation of chlorins as potential photosensitizers for PDT. This report describes the evaluation of a new water-soluble formulation of chlorin e6 consisting of a complex of trisodium salt chlorin e6 and polyvinylpyrrolidone (Ce6-PVP) for application in photodynamic therapy (PDT) with 2 specific aims: (i) to investigate its fluorescence kinetics in skin, normal and tumor tissue after intravenous administration, and (ii) to investigate its PDT efficacy. Our results demonstrate that this new formulation possesses photosensitizing properties with rapid accumulation in tumor tissue observed within 1 h after intravenous administration. Although high selectivity in tumor tissue was found between the period of 3 and 6 h, the efficacy of Ce6-PVP mediated PDT was best at 1 h drug-light interval. It is suggested that, the extent of tumor necrosis post PDT is dependent on the plasma concentration of Ce6-PVP, implying a vascular mediated cell death mechanism. A faster clearance rate of Ce6-PVP from the skin of nude mice was observed compared to Ce6. The new formulation of Ce6-PVP seems to show promise as an effective therapeutic agent.

Animals↗
PubMed2000

Anaphylaxis to polyvinylpyrrolidone in an analgesic preparation.

A 32-year-old patient developed an anaphylactic reaction minutes after oral intake of acetaminophen-containing tablets (Doregrippin)). Scratch testing of the whole preparation was positive in contrast with the negative results obtained with pure acetaminophen. Therefore, scratch tests with the remaining drug components were performed and showed polyvinylpyrrolidone (PVP) to be the aetiological agent. Furthermore, specific IgE antibodies against PVP were demonstrated using a dot blot technique, thus ruling out a pseudo-allergic reaction. This case underlines the necessity to consider not only the active ingredient, but also additives as the causative agent.

Acetaminophen↗
PubMed2006

Molecular dynamics and interactions of aqueous and dichloromethane solutions of polyvinylpyrrolidone.

We have investigated the dynamics of polyvinylpyrrolidone solutions (PVP, M(w)=10 000) on time scales from 20 fs to 42 ps using femtosecond optically heterodyne-detected Raman-induced Kerr effect spectroscopy. To compare the dynamics of polymer solutions with those of the analogous monomer, we also characterized solutions of 1-ethyl-2-pyrrolidone (EP). Dynamics of both PVP and EP solutions have been characterized for sample concentrations of 6.4, 12.7, 24.5, 33.3, and 40.7 wt %. The longest time scale relaxations observed in the Kerr transients for these solutions occur on the picosecond time scale and are best fit to triexponential functions. The intermediate and slow relaxation time constants for PVP and EP solutions are concentration dependent. The time constants for the PVP solutions are not consistent with the predictions of hydrodynamic models, while the analogous time constants for the EP solutions do display hydrodynamic scaling. The predominant relaxation of the polymer is assigned to reorientations of the pyrrolidone side group or torsional motions of the constitutional repeat unit, with additional relaxation pathways including hydrogen bond reorganization in aqueous solution and segmental motion of multiple repeat units. The vibrational dynamics of PVP and EP solutions occur on the femtosecond time scale. These dynamics are analyzed with a focus on the additional degrees of freedom experienced by EP relative to PVP that result from the absence of the tether from the pyrrolidone group on the main chain backbone. The intermolecular Kerr spectra of PVP in H(2)O and CH(2)Cl(2) differ because H(2)O can donate a hydrogen bond to the carbonyl acceptor group on the pyrrolidone ring, while CH(2)Cl(2) cannot.

Journal Article↗
PubMed2006

Polyvinylpyrrolidone 40 assists the refolding of bovine carbonic anhydrase B by accelerating the refolding of the first molten globule intermediate.

Protecting proteins from aggregation is one of the most important issues in both protein science and protein engineering. In this research, the mechanism of enhancing the refolding of guanidine hydrochloride-denatured carbonic anhydrase B by polyvinylpyrrolidone 40 (PVP40) was studied by both kinetic and equilibrium refolding experiments. The reactivation and refolding kinetics indicated that the rate constant of refolding the first refolding intermediate (I(1)) to the second one (I(2)) is promoted by the addition of PVP. Fluorescence quenching studies further indicated that PVP could bind to the aggregation-prone species I(1), resulting in the protection of the exposed hydrophobic surface, a minimization of the protein surface, and more importantly, an increase of the refolding rate of I(1). These properties were quite different from those of poly(ethylene glycol) (PEG), which has been shown to have a strong and stoichiometric binding to I(1) and does not interfere with the refolding pathway. Unlike PEG, the binding of PVP to I(1) does not block the aggregation pathway directly but decreases the energy barrier for I(1) to refold to I(2) and thus reduces the accumulation of I(1). These results suggested that PVP works by a quite different mechanism from those well established ones in chaperones and chemical promoters. PVP is more like a folding catalyst rather than a chemical chaperone. The distinct mechanism of enhancing protein aggregation by PVP is expected to facilitate the attempt to develop new chemical compounds as well as new strategies to protect proteins from aggregation.

Animals↗
PubMedDate not supplied

Individual cryopreservation with dimethyl sulfoxide and polyvinylpyrrolidone of ejaculates and pooled semen of three avian species.

Artificial insemination (AI) has been used for avian reproduction due to the discovery of cryoprotectants extending its usefulness both in production of domestic fowl and conservation of wild species. The goal of this study was to assess the effect on domestic and wild fowl pooled semen and individual ejaculate cryopreservation with dimethyl sulfoxide (DMSO) and polyvinylpyrrolidone (PVP). Twenty ejaculates and twenty samples of pooled semen of roosters, pheasants and hawks were frozen in media containing DMSO or PVP. DMSO and PVP cryopreservation are equally effective both for ejaculates and pooled semen. Even PVP is a good alternative since no significant difference was found when compared to DMSO. The fertilizing capacity of fresh and cryopreserved pooled semen was analyzed through AI of hens and female pheasants. Similar fertility rates using DMSO, PVP or frozen-thawed samples demonstrated that reproduction is possible through the use of cryopreserved semen. In the case of female pheasants, the same values were obtained with both cryopreserved and fresh semen.

Animals↗
PubMed2005

Miscibility behavior and formation mechanism of stabilized felodipine-polyvinylpyrrolidone amorphous solid dispersions.

In the present study, solid dispersion systems of felodipine (FEL) with polyvinylpyrrolidone (PVP) were developed, in order to enhance solid state stability and release kinetics. The prepared systems were characterized by using Differential Scanning Calorimetry, X-Ray Diffraction, and Scanning Electron Microscopy techniques, while the interactions which take place were identified by using Fourier Transformation-Infrared Spectroscopy. Due to the formation of hydrogen bonds between the carbonyl group of PVP and the amino groups of FEL, transition of FEL from crystalline to amorphous state was achieved. The dispersion of FEL was found to be in nano-scale particle sizes and dependent on the FEL/PVP ratio. This modification leads to partial miscibility of the two components, as it was verified by DSC and optimal glass dispersion of FEL into the polymer matrix since no crystalline structure was detected with XRD. The above deformation has a significant effect on the dissolution enhancement and the release kinetics of FEL, as it causes the pattern to change from linear to logarithmic. An impressive optimization of the dissolution profile is observed corresponding to a rapid release of FEL in the system containing 10% w/w of FEL, releasing 100% in approximately 20 min. The particle size of dispersed FEL into PVP matrix could be classified as the main parameter affecting dissolution optimization. The mechanism of such enhancement consists of the lower energy required for the dissolution due to the amorphous transition and the fine dispersion, which leads to an optimal contact surface of the drug substance with the dissolution media. The prepared systems are stable during storage at 40 +/- 1 degrees C and relative humidity of 75 +/- 5%. Addition of sodium docusate as surfactant does not affect the release kinetics, but only the initial burst due to its effect on the surface tension and wettability of the systems.

Differential Thermal Analysis↗
PubMed2006

Enhancement of the dissolution and permeation rates of meloxicam by formation of its freeze-dried solid dispersions in polyvinylpyrrolidone K-30.

Freeze-drying (FD) and solvent evaporation (SE) were used to prepare solid dispersions (SDs) of meloxicam (MX) in polyvinylpyrrolidone K-30 (PVP). The SDs were prepared at different ratios, namely 1:1, 1:3, and 1:5 MX:PVP weight ratio. Differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), and x-ray powder diffractometry (XPD) were utilized to characterize the physicochemical properties of the SDs. Meloxicam (MX) in the solid dispersions appeared with less crystallinity form and was present in a complete amorphous form at higher PVP ratio. Dissolution rates of MX as a pure drug, physical mixtures (PMs), and SDs indicated a marked increase of the dissolution rate of MX in presence of PVP. The increase in the dissolution rate was dependent on the ratio of PVP and the method of preparation. In addition, the permeability of the drug through standard cellophane membrane and hairless mouse skin was also evaluated. The permeation rate of MX was significantly increased in the case of SDs and was dependent on the ratio of PVP. The results were primarily due to increase wettability, the solubilization of the drug by the carrier, and formation of MX amorphous form.

Animals↗
PubMed2001

A physiological replacement for polyvinylpyrrolidone (PVP) in assisted reproductive technology.

The technique of intracytoplasmic sperm injection (ICSI) requires mechanical immobilization of the sperm that are to be injected; damage thus caused to the sperm membrane is considered to be necessary to activate the sperm for fertilization. Mechanical immobilization and the injection procedure are facilitated by introducing the sperm into a viscous medium that will hinder motility: a solution of polyvinylpyrrolidone (PVP) has been used successfully for this purpose. PVP is an artificial polymer, which has been regarded as chemically inert, although adverse effects have been reported as a result of its use both in vivo and in vitro. Therefore, the use of hyaluronate, the natural component of the extracellular matrix of the cumulus-oocyte complex, was investigated as a replacement for PVP during ICSI. A solution of hyaluronate was found to be as effective as PVP in facilitating the injection procedure, its effect on sperm motility was readily reversible, and its use did not affect the outcome of the treatment cycles in terms of fertilization, pregnancy and live birth rates. Every attempt should be made to eliminate artificial factors in assisted reproductive procedures. Hyaluronate, a natural and readily degradable glycosaminoglycan can be used as a substitute for the artificial PVP polymer without jeopardising the outcome of the treatment cycle.

Adult↗
PubMed2003

Increasing the aqueous solubility of acetaminophen in the presence of polyvinylpyrrolidone and investigation of the mechanisms involved.

It was shown that the aqueous solubility of acetaminophen in the presence of polyvinylpyrrolidone (PVP) increased. The solubility at 25 degrees C increased from 14.3 m mL(-1) in the absence of PVP, to 19.7 mg m(-1) in the presence of 4% w/v PVP, and to 26.7mg mL(-1) in the presence of 8% w/v PVP. Dialysis studies indicated that there is a potential of binding between PVP and acetaminophen in their aqueous solutions. Dialysis studies also revealed that the nature of interaction between PVP and acetaminophen is physical and reversible, and there was no strong binding between PVP and acetaminophen in their solutions. Infrared spectroscopy of acetaminophen/PVP solid dispersion indicated that the mechanism of interaction between PVP and acetaminophen is via hydrogen bonding. Therefore, the increase in solubility of acetaminophen in the presence of PVP is probably attributed to its ability to form a water-soluble complex with PVP.

Acetaminophen↗
PubMed2001

Interpolymer complexation. II. Entrapment of ibuprofen by in-situ complexation between polyvinyl acetate phthalate (PVAP) and polyvinylpyrrolidone (PVP) and development of a chewable tablet formulation.

A new method involving in situ complexation between polyvinyl acetate phthalate (PVAP) and polyvinylpyrrolidone (PVP) has been developed for the entrapment of ibuprofen, a bitter tasting anti-inflammatory drug. The procedure involved dissolving ibuprofen in a thoroughly mixed aqueous alkaline solution of PVAP and PVP, and subsequently slowly adjusting the pH of the solution to 1 with dilute HCl. The yield of the entrapped product, and the percent entrapment of ibuprofen, were 85-90%, and 90-98%, respectively. The PVAP-PVP entrapped granules showed no bitter taste due to ibuprofen. The chewable tablets, prepared by mixing the granules with a cherry-flavored directly compressible tableting excipient, exhibited a release of less than 2% of ibuprofen in pH 1.2 buffer over a period of three hours. In pH 7.4, 100% of ibuprofen was released in six hours. The results presented show that in situ complexation between PVAP and PVP may be useful to produce palatable ibuprofen granules suitable for use in the development of chewable tablets.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Roller compaction of crude plant material: influence of process variables, polyvinylpyrrolidone, and co-milling.

Roller compaction of a milled botanical (Baphicacanthus cusia) with and without a binder, polyvinylpyrrolidone (PVP) was conducted. Effects of co-milling on binder function and flowability of the powder blend was also investigated. Flakes were comminuted, and the size and size distribution, friability, Hausner ratio, and Carr index of the granulations were determined. Crude herb should be reduced to a suitable size for it to be successfully roller compacted. Larger-sized and less friable granules were obtained with decreasing roller speed. Addition of PVP affected the flowability and binding capacity of the herbal powder blend, which influenced size and friability of the granules. Co-milling of PVP with the herbal powder enhanced the flow of the blends and the effectiveness of the binder, which contributed favorably to the roller-compacted product. Roller compaction is a convenient and cost-effective granulating technique suitable for milled botanicals. Co-milling can be used to improve the properties of roller-compacted products.

Apocynaceae↗
PubMed1985

Regulation of IgG memory responses by helper and suppressor T cells activated by the type 2 antigen, polyvinylpyrrolidone.

T cells from CAF1 mice immunized with various amounts of the type 2 antigen polyvinylpyrrolidone (PVP) were assessed for their ability to provide help to PVP-specific memory B cells for the production of IgG. Low doses (0.0025 micrograms) of PVP consistently activated helper T cells (Th), which were required for the production of IgG by primed B cells. In contrast, T cells from mice primed with higher amounts (0.25 or 25 micrograms) of PVP did not provide significant help to the same B cells for IgG production. Moreover, when mixed with B cells and low-dose PVP-primed Th, T cells from mice primed with 0.25 or 25 micrograms PVP suppressed PVP-specific IgG, but not IgM antibody responses. The suppressor cells induced by higher amounts of PVP were eliminated either by injecting cyclophosphamide (CY) before priming with PVP, or by treating the primed T cells with anti-Lyt-2.2 and C before transfer. Pretreatment of suppressor T cell (Ts) donors with CY or removal of Lyt-2+ T cells not only eliminated Ts activity, but also unmasked significant Th activity in the T cells from high-dose PVP-primed mice. Thus, both low and high amounts of PVP can activate Th, although high amounts of PVP also induce Ts, the activity of which predominates in a normal unfractionated T cell population. The amount of PVP (0.0025 micrograms) that induces dominant help for IgG memory responses was only marginally immunogenic for induction of primary PVP-specific IgM responses, while 0.25 and 25 micrograms PVP, which induce dominant suppression for IgG memory responses, are optimally immunogenic for primary IgM responses. These results are discussed in the context of the inability of most type 2 antigens to elicit primary IgG responses or to prime memory B cells for production of IgG, responses which are dependent on the function of antigen-specific Th.

Animals↗