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Biomedical subjects

P York

Publications and source records attributed to P York.

18 recordsLinked to original sources
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↗
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↗
PubMed1978

Particle slippage and rearrangement during compression of pharmaceutical powders.

Compression data from different size fractions of lactose, chloroquine diphosphate, stearic acid and calcium carbonate have been analysed using the Walker and the Heckel compression equations. Points of inflection in graphs of log applied pressure vs the reciprocal of the packing fraction at low pressures corresponded closely to figures for theoretical packing conditions for equisized spheres and are attributed to a change in the stage of compression. The degree of particle slippage and rearrangement taking place during compression has been shown to increase as the particle size of the powder decreases and to be more extensive for powders composed of non-spherical particles. In addition, three types of compression behaviour have been distinguished for the four powders studied.

Calcium Carbonate↗
PubMed1977

Dimensional changes of compacts after compression.

A non-contact optical technique has been used to measure changes in the heights and diameters of compacts prepared from sodium chloride, spray dried lactose, two samples of methylcellulose powder and two spray-dried lactose-maize starch granulations. Both sodium chloride and spray dried lactose exhibited relatively small dimensional changes whilst the methylcellulose powders showed up to 30% axial and 3% radial expansion. The results are discussed in terms of the inherent properties of the materials. When the lactose was granulated with maize starch, the ratio of axial; radial strain recovery was reduced from 5-9:1 to approximately 1:1, suggesting an improved distribution of forces during compression of the granulations,

Drug Compounding↗
PubMed1977

The shelf life of some antibiotic preparations stored under tropical conditions.

Accelerated storage tests have been carried out to predict the shelf life of several commercial preparations stored directly under temperate and tropical climatic conditions. Two brands each of sulphathiazole tablets, tetracycline hydrochloride capsules and chloramphenicol capsules were studied over a period of three months. Shelf lives ranging from 6.2. to 29.7 months were predicted for temperate storage conditions (20 degree C/31% R.H.), whilst these periods were reduced giving values from 3.8 to 13.9 months for tropical conditions of 30 degree C/31% R.H and from 2.5 to 9.2. months when stored at 30 degree C/75% R.H. A decrease in the rate of drug dissolution was also observed for preparations stored directly under conditions of elevated temperature and humidity. The results indicate the need for stringent control over storage conditions for antibiotic preparations in tropical climates to ensure adequate drug stability and dissolution characteristics.

Anti-Bacterial Agents↗
PubMed1976

Modification of diffusion rates of benzocaine from topical vehicles using sodium salicylate as complexing agent.

The release of benzocaine from various topical vehicles containing benzocaine, alone and in the presence of a complexing agent, sodium salicylate, was measured at 37 degrees using dialysis through a cellulose membrane. Sodium salicylate had a marked effect on the release of benzocaine, depending upon the the type of vehicle, with the largest increase observed for the water-miscible base, polyethylene glycol (macrogol ointment BPC). The amount of drug released from preparations containing 1% (w/w) and 2% (w/w) benzocaine in this vehicle depended upon the sodium salicylate concentration. Results are discussed in terms of the differing physical properties of the complexes formed.

Benzocaine↗
PubMed1976

A preliminary study of the physical stability of tablets prepared from powders stored under tropical conditions.

A study has been made of the effects of storing powders under tropical conditions before compression on the physical stability of the tablets prepared from them, as measured by changes in tablet weight, volume and hardness. Significant changes in stability have been observed and these have been related to the different degrees of moisture uptake by the powders during storage. In addition, the initial powder storage conditions have been shown to be important when considering the best method of tablet manufacture with respect to tablet stability.

Drug Stability↗
PubMed1975

Application of powder failure testing equipment in assessing effect on glidants on flowability of cohesive pharmaceutical powders.

Powder failure testing equipment was used successfully to study the effect of glidants on the flowability of two cohesive pharmaceutical powders, lactose and calcium hydrogen phosphate, using the flow factor as the flowability parameter. Fine silica, magnesium stearate, and purified talc were investigated as glidants; for each host powder-glidant mixture, an optimum concentration of glidant was observed beyond which no further increase in flowability occurred. The order of efficiency of glidants for both host powders was fine silica greater than magnesium stearate greater than purified talc. The mode of action of the three glidants is discussed.

Calcium Phosphates↗