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Biomedical subjects

P York

Publications and source records attributed to P York.

At least 55 records · Page 3Linked to original sources
PubMed1995

Characterization of wet powder masses with a mixer torque rheometer. 3. Nonlinear effects of shaft speed and sample weight.

We used mixer torque rheometry to examine the effects of shaft speed and sample weight on the rheological behavior of a model wet mass consisting of microcrystalline cellulose and water. Both variables contribute differently to the measured parameters of mean torque and torque range (amplitude). For small weights, the effect of shaft speed is small, but for large weights, shaft speed has a greater effect. For large sample weights, the effect of shaft speed on measured mean torque can be modeled by the Herschel-Buckley model originally developed for concentrated dispersions, enabling yield stresses and viscosities to be calculated. The data generated compare favorably with those measured previously by capillary rheometry.

Cellulose↗
PubMed1994

Solid-state properties and crystal structure of gliclazide.

The solid-state characterization of gliclazide, for which no analytical standard was previously available, has been completed by extensive structural and physical analytical examination. The crystal and molecular structure for gliclazide was determined by single-crystal X-ray diffraction. Gliclazide crystallizes in the monoclinic space group P2(1)/n, with the unit cell dimensions a = 10.828(2) A, b = 14.342(19) A, c = 11.005(6) A, and with beta = 106.97(2) degrees, V = 1635(12) A3, and Z = 4. The gliclazide molecule is articulated in an open extended conformation about the sulphonylurea nucleus. Two gliclazide molecules form a complex with one calcium atom to facilitate the transport of calcium ions across the pancreatic beta cells necessary for the stimulation of insulin secretion. The only conformation that allows for the close apposition of the tolyl groups, and therefore the formation of the gliclazide:calcium complex, is the extended conformer.

Calorimetry, Differential Scanning↗
PubMed1993

Destabilizing effects of replacing a surface lysine of cytochrome c with aromatic amino acids: implications for the denatured state.

A series of mutations at the highly solvent-exposed lysine 73 of iso-1-cytochrome c have been prepared by site-directed mutagenesis. These mutations were designed to probe denatured-state effects on the unfolding equilibrium of this protein. The hydrophilic amino acid Lys was replaced with the hydrophobic amino acids Met, Tyr, Phe, and Trp. The idea was to induce stabilizing hydrophobic interactions in the unfolded state, while having little effect on the folded-state energy due to the high solvent exposure of this site. Fourier transform infrared spectral analyses indicate that none of these mutations significantly affect the native fold of the protein. The stability of each protein to guanidine hydrochloride denaturation was monitored at 25 degrees C by circular dichroism spectroscopy. All four hydrophobic mutants decreased the value of delta Go uH2O, the free energy of unfolding of the protein in the absence of denaturant, by 1.0-1.5 kcal/mol. The delta Go uH2O values for these proteins correlate linearly (correlation coefficient of 0.98) with the hydrophobicity of the amino acid at position 73 of the sequence. These data are consistent with the idea that the position-73 mutants are more buried in the denatured state than in the native state, suggestive of a compact denatured state where such interactions would be possible.

Base Sequence↗
PubMed1992

Physicochemical properties of salts of p-aminosalicylic acid. I. Correlation of crystal structure and hydrate stability.

The potassium (K), sodium (NA), calcium (CA), and magnesium (MG) salts of p-aminosalicylic acid were obtained, and their thermal behavior was characterized by means of differential scanning calorimetry (DSC) and thermogravimetric analysis (TG). Their crystal and molecular structures were determined by single-crystal X-ray diffraction after powder patterns had shown them to be nonisomorphous. Different degrees of hydration were observed for the solid salts, and an assessment of hydrate stability to dehydration was made from thermogravimetric studies. The onset temperature of dehydration (Tt) of each salt varied within the series and exhibited correlation with X-ray determined structure. The observed onset of dehydration of MG and CA was higher than that of NA and is consistent with stronger ion-dipole interactions for the divalent salts. Crystallographic determination of the bond lengths between the metal ion and the water oxygens were 2.4 and 2.9 A for NA, between 2.0 and 2.1 A for MG, and 2.4 A for CA. The open nature and presence of a channel feature in the structure of the sodium salt may have facilitated escape of water molecules from the crystal. Particle presentation (e.g., size, crystallinity) was also shown to affect dehydration behavior.

Aminosalicylic Acid↗
PubMed1991

Improved bioavailability from a spironolactone beta-cyclodextrin complex.

The relative bioavailabilty of spironolactone from a complex with beta-cyclodextrin has been evaluated. Capsules containing 100 mg micronised spironolactone powder were compared with 100 mg spironolactone beta-cyclodextrin complex in 8 healthy volunteers by a single dose, double blind, crossover pharmacokinetic study. Subjects were randomly allocated to each preparation and crossed over after 2 weeks. Relative bioavailability was assessed by the measurement of serum canrenone concentrations. The mean relative bioavailability of the spironolactone cyclodextrin complex, compared to the micronised spironolactone powder, was 233%. Statistical analysis (Wilcoxon signed rank test) revealed that this difference was significant with a mean area under the serum concentration time curve of 3.90 and 1.88 mg.h.l-1 for the complex and micronised spironolactone powder, respectively. Four of the volunteer also received a 100 mg spironolactone tablet (Aldactone) under identical conditions. Pharmacokinetic analysis revealed that the mean relative bioavailability of the spironolactone beta cyclodextrin complex and micronised powder when compared with spironolactone tablets (Aldactone) was 252% and 124%, respectively. There was no change in the canrenone elimination half lives of each subject.

Adult↗
PubMed1989

Thermal characterization of drug/polymer and excipient/polymer interactions in some film coating formulation.

Some probable consequences of the dissolution/migration of a major solid dosage component in or into an applied film coating during or after a film coating operation have been investigated using free films of hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) incorporating small amounts of either lactose (a diluent) or ephedrine hydrochloride (a drug). Intrinsic features of the films such as softening, glass transition, crystallinity and melting were examined by differential scanning calorimetry and thermomechanical analysis. Generally, the results indicate that ephedrine hydrochloride exhibited plasticizing activity in both HPMC and PVA films. On the other hand, incorporation of lactose produced an opposite effect (stiffening) in PVA films as demonstrated by increased glass transition temperature and crystallinity. On the basis of these findings, it was proposed that the undesired presence of a component of a solid dosage core in the applied film coating could significantly alter its end-use properties such as diffusivity and the incidence of film coating defects. It was also shown that the application of the relationship of Moelter & Schweizer (1949) in the evaluation of the plasticizer efficiency of non-homologous additives could pose problems of interpretation.

Chemistry, Pharmaceutical↗
PubMed1989

The in-vitro pH-dissolution dependence and in-vivo bioavailability of frusemide-PVP solid dispersions.

The dependence of the dissolution rate on the pH of the buffered medium, using constant surface area discs, has been examined for crystalline frusemide, a semi-crystalline frusemide-polyvinylpyrrolidone (PVP) solid dispersion and an X-ray amorphous frusemide-PVP dispersion. The marked changes observed in the pH-dissolution profiles indicate that differing dissolution mechanisms operate in the amorphous regions. This conclusion was further supported by the comparison of pH-dissolution and pH-equilibrium solubility profiles that suggested a supersaturation effect to be the relevant term in describing the dissolution enhancing effects of amorphous regions. A marked dissolution enhancement, relative to crystalline frusemide, was shown by the X-ray amorphous solid dispersion in weakly acidic solutions. A similar effect was observed in the dissolution characteristics of gelatin capsule formulations in simulated gastric and intestinal media. In a human bioavailability study, the X-ray amorphous frusemide-PVP solid dispersion exhibited a significant reduction in the time for maximum effect in comparison to crystalline frusemide and a semi-crystalline solid dispersion. This effect, demonstrated by the primary end organ response in seven healthy subjects, concurred with the in-vitro prediction of dissolution enhancement in weakly acidic media.

Adult↗
PubMed1988

Studies of interaction phenomena in aqueous-based film coatings containing soluble additives using thermal analysis techniques.

Interaction phenomena, in aqueous-based hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) film-coating formulations containing water-soluble additives (citric acid and urea) have been examined by thermal methods to assess glass transition, softening, melting, plasticization, and crystallinity. The methods used were differential scanning calorimetry (DSC) and thermomechanical analysis (TMA) in penetration and expansion modes. In addition to the established thermal transitions occurring in HPMC and PVA at relatively high temperatures, transitions were also observed between 26 and 43 degrees C using TMA. These low temperature transitions, unlike those occurring at the higher temperatures, were low energy transitions and not influenced by the type and concentration of the additives incorporated. The results also showed that the plasticizing activities of citric acid and urea were as high as those of some currently used plasticizers. On a weight basis, urea was superior to citric acid as a plasticizer for either HPMC or PVA, but when their molar contents were considered, the position was reversed. Also, PVA crystallinity was depressed in the presence of the additives.

Calorimetry, Differential Scanning↗
PubMed1987

Evidence for solid- and liquid-state interactions in a furosemide-polyvinylpyrrolidone solid dispersion.

The solid-state interactions between furosemide (FUR) and polyvinylpyrrolidone (PVP) in a solid dispersion system have been investigated by dispersive and Fourier Transform IR. Using spectral subtraction procedures, shifts to lower frequencies are seen in FUR-NH stretching vibrations in amorphous FUR-PVP systems in comparison with the crystalline FUR spectrum. The magnitude of shifts are similar to those seen when FUR is dissolved in the hydrogen-bonding solvent 1,4 dioxan (0.015-0.155 M, 20 degrees C). Spectral assignment indicates the FUR sulfonamide group binds to PVP in preference to the FUR secondary amine which is shown to possess an intramolecular hydrogen bond by analysis of published X-ray crystal data. With a molecular graphics computer program, the FUR crystal unit cell was compiled, and analyses of nonbonded intermolecular distances are useful in interpreting IR shift data in amorphous solid dispersions. A study of FUR-PVP interactions in solution, examined by proton NMR, reveals a downfield shift of the FUR sulfonamide proton resonance. This shift exhibits dilution and temperature (298-338 K) dependence consistent with an intermolecular hydrogen bond. The secondary amine proton resonance exhibits temperature but not dilution or solvent bonding potential dependence, characteristics of an intramolecular hydrogen bond. The proposed hydrogen bond FUR-PVP interaction may account for the formation and stabilization of the amorphous solid dispersion.

Furosemide↗
PubMed1986

Mechanical properties of some pigmented and unpigmented aqueous-based film coating formulations applied to aspirin tablets.

The Brinell hardness and Young's modulus of pigmented and unpigmented films of hydroxypropyl methylcellulose alone, and in combination with either polyethylene glycol 400 (plasticizer) or polyvinyl alcohol, which were applied to aspirin tablets, have been measured. Generally hardness and modulus data showed similar trends. The hardness and modulus of hydroxypropyl methylcellulose fell in the presence of polyethylene glycol 400 as a result of its plasticizing action. On the other hand, the hardness and modulus of the film former rose slightly when polyvinyl alcohol was initially incorporated, probably due to the crystalline phase of the additive, and then decreased when the level of the additive was further raised. Hardness and modulus were higher in films pigmented with talc than in those containing titanium dioxide because of the plate-like shape of talc and its greater interaction with the polymer systems. Some correlation was found between the Young's moduli of the applied films and those of the corresponding free films, with the moduli of the latter two 2-5 times greater. Ageing at 37 degrees C and 75% r.h. was found to cause a decrease in the mechanical properties of the unplasticized film coating systems probably as a result of decreased molecular order and enhanced polymer chain mobility.

Aspirin↗
PubMed1985

Characterization of moisture interactions in some aqueous-based tablet film coating formulations.

Three methods--radiotracer, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)--have been employed to evaluate moisture interactions in aqueous-based hydroxypropyl methylcellulose films containing polyethylene glycol 400, polyethylene glycol 1000 or polyvinyl alcohol. The radiotracer employed was tritiated water. Using a proposed classification, the water present in the films was placed in three categories: tightly bound, moderately bound and free. The tightly bound water in hydroxypropyl methylcellulose and hydroxypropyl methylcellulose/polyvinyl alcohol films was related to the crystallinity of the films whilst tightly bound water was practically non-existent in the plasticized systems thus indicating the absence of crystallinity. Free (or freezable) water could not be detected in the films using DSC. The moisture content data obtained by TGA were considered to represent moderately bound water. The moderately bound water content of the film systems was in the rank order of the hydrophilicity of the polymer additives: polyethylene glycol 400 greater than polyethylene glycol 1000 greater than polyvinyl alcohol. This order was reversed for the calculated free water content.

Calorimetry, Differential Scanning↗
PubMed1985

Stress crack resistance of some pigmented and unpigmented tablet film coating systems.

Stress crack resistance parameters--tensile strength: Young's modulus ratio, relative surface energy, and toughness index--have been examined for unpigmented free films of hydroxypropyl methylcellulose containing polyvinyl alcohol, and polyethylene glycols 400 and 1000, as well as similar film systems pigmented with either talc or titanium dioxide. Incorporation of either polyvinyl alcohol or polyethylene glycols 400 and 1000 in hydroxypropyl methylcellulose film coatings eliminated the incidence of edge splitting in the coated tablets. Increase in pigment concentration generally led to a decrease in the crack resistance of pigmented films. There was a relation between the stress crack resistance of pigmented free films and the incidence of edge splitting of corresponding film coatings applied to aspirin tablets--generally, the higher the crack resistance the lower the incidence of edge splitting. A similar relationship applied to the unpigmented films only when the tensile strength: Young's modulus ratio was considered.

Aspirin↗
PubMed1985

Tensile anisotropy of some pigmented tablet film coating systems.

The tensile properties of representative tablet film coating systems, containing hydroxypropyl methylcellulose alone and in combination with either polyvinyl alcohol, polyethylene glycol 400 and polyethylene glycol 1000 and pigmented with either talc or titanium dioxide, have been investigated. Tensile anisotropy was observed between film samples cut parallel to, and perpendicular to, the direction of rotation of the casting substrate and factors accounting for this phenomenon are presented.

Chemistry, Pharmaceutical↗
PubMed1985

The adhesion characteristics of some pigmented and unpigmented aqueous-based film coatings applied to aspirin tablets.

The adhesion of pigmented (with talc and titanium dioxide) and unpigmented aqueous-based films, derived from hydroxypropyl methylcellulose, to aspirin tablets and the effect of ageing on the measured adhesion have been assessed. The adhesion of hydroxypropyl methylcellulose film attained maximum values at polyethylene glycol 400 and polyvinyl alcohol levels of 10 and 20 wt%, respectively. Above these concentrations, adhesion decreased. For solid loaded films it is proposed that the effect of pigments on film adhesion is dependent on the balance between their influence on the internal stress of the film coating and the strength of the film-tablet interface. Adhesion was enhanced when a pigment increased the strength of the interface faster than it increased internal stress, and vice versa. A simple relation between the measured adhesion and the incidence of edge splitting of film-coated tablets was not observed. Generally, film adhesion fell when the tablets were aged at 37 degrees C and 75% r.h. as a result of swelling-induced stresses in the film and at the film tablet interface. The effect of ageing on the adhesion of the system plasticized with polyethylene glycol 400 was eased when the film was pigmented. Adhesion was largely unaffected with film-coated tablets stored in tightly closed bottles at 20 degrees C for five months.

Aspirin↗
PubMed1983

Analysis of the permeation and mechanical characteristics of some aqueous-based film coating systems.

The moisture permeability and mechanical properties of some aqueous-based free films have been evaluated using sorption-desorption and stress-strain techniques, respectively. These properties for blends of two film-formers--hydroxypropyl methylcellulose and polyvinyl alcohol--have been compared with those of hydroxypropyl methylcellulose films plasticized with polyethylene glycols. The polyethylene glycols generally increased the moisture permeability of hydroxypropyl methylcellulose films while polyvinyl alcohol decreased it. Both polyvinyl alcohol and the polyethylene glycols lowered tensile strength at break and Young's modulus but the effects of the polyethylene glycols were more pronounced. These results are discussed in terms of structural interactions between film components. All film systems evaluated, except that containing hydroxypropyl methylcellulose alone, exhibited a degree of anisotropy, a phenomenon with potentially adverse consequences in tablet film coating.

Chemistry, Pharmaceutical↗
PubMed1981

Analysis of moisture sorption hysteresis in hard gelatin capsules, maize starch, and maize starch: drug powder mixtures.

Moisture sorption and desorption isotherms at 25 degrees C for hard gelatin capsules, maize starch and 50:50 mixes of maize starch: barbitone and maize starch: sodium barbitone have been measured. The sorption hysteresis observed in all four systems studied has been analysed according to the hypothesis of Young & Nelson (1967a) which distinguishes three locations for moisture--monolayer adsorbed moisture, normally condensed moisture and absorbed moisture. Hysteresis is explained by a separation of absorption and desorption isotherms for absorbed moisture and different patterns of moisture distribution are demonstrated in the four systems examined.

Adsorption↗