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Biomedical subjects

J W McGinity

Publications and source records attributed to J W McGinity.

At least 55 records · Page 3Linked to original sources
PubMed1980

Subcutaneous silastic implants: maintenance of high blood ethanol levels in rats drinking a liquid diet.

A new subcutaneous form of ethanol exposure in rats is described. The Sustained Ethanol Release Tube (SERT) for rats is similar to an earlier device reported for mice, except that only one refill per day is required. This device, plus an intragastric loading dose for initially raising blood ethanol levels (BEL), is capable of maintaining high BEL for greater than 12 hours. Supplementation of SERT-released ethanol with a Sustacal chocolate-flavored diet with 37% of total energy as ethanol produces high, stable BEL for indefinite periods. Maintenance of such BEL for 9 days is sufficient to cause dramatic withdrawal signs when ethanol exposure is stopped. The method is useful as a model for conveniently and quickly producing physical dependence to ethanol in rats.

Animals↗
PubMed1979

Effect of water-soluble carriers on morphine sulfate release from a silicone polymer.

The influence of gelatin, sodium lauryl sulfate, lactose, and sodium alginate on morphine sulfate diffusion from cylindrical silicone polymer pellets was examined in isotonic pH 7.4 phosphate buffer. These water-soluble carriers caused the pellets to swell in aqueous media. Sodium alginate exerted the greatest influence on drug release. The morphine sulfate diffusion rate from the cylindrical pellets increased as the matrix alginate content increased up to 20%. Water-soluble carrier incorporation into silicone polymeric matrixes permits controlled release of water-soluble drugs that otherwise would be released extremely slowly from the polymer. Drug diffusion from the silicone matrix containing sodium alginate followed second-order kinetics. The release mechanism probably involves the creation of pores or pathways through the matrix secondary to the swelling.

Delayed-Action Preparations↗
PubMed1978

Sustained release of alcohol: subcutaneous silastic implants in mice.

A sustained-release device for use in ethanol dependence studies in mice is described. The Silastic device, dubbed SERT (sustained ethanol release tube), holds 0.35 milliliter of 95 percent ethanol (by volume) and is implanted under the skin of the back where it releases ethanol for up to 12 hours, with no observable tissue damage. The device may be adaptable to the release of other volatile liquids or drugs, in other animals.

Alcoholic Intoxication↗
PubMed1978

Preparation and evaluation of a sustained morphine delivery system in rats.

A new drug delivery system to induce physical dependence to morphine in rats is described. The device consists of a silicone polymer containing a water soluble "carrier" material, sodium alginate, which swells on contact with moisture to release the drug. The silicone or silastic pellets formulated to contain morphine sulfate are very easily prepared and the advantages over existing methods to induce physical dependence to morphine are discussed. In addition, a comparison of the percent of drug released and withdrawal intensities in rats was made with a silastic-morphine sulfate pellet, silastic-morphine base pellet and a microcrystalline cellulose-morphine base pellet.

Animals↗
PubMed1977

Sustained-release applications of montmorillonite interaction with amphetamine sulfate.

Urinary recovery studies showed that montmorillonite significantly affects the initial therapeutic levels of amphetamine sulfate. The combination of a 1:20 drug-montmorillonite complex with pure drug in a 1:1 ratio, based on amphetamine content, resulted in recovery profiles resembling those obtained from prolonged-release dosage forms. The 1:20 complex, pure drug, and combination formulations showed comparable bioavailability after 48 hr.

Adult↗
PubMed1977

Chronic administration of cyanide: urinary excretion of thiocyanate in male and female rats.

The urinary elimination of thiocyanate was investigated in male and female rats following the chronic administration of potassium cyanide. Female rats dosed at the level of 5 mg KCN/kg once a week and twice a week respectively, displayed no significant difference in the excretion of thiocyanate in urine after periods of up to eight weeks of study. Similarly, male rats that were administered 5 mg/KCN/kg twice weekly showed no significant difference in the amount of thiocyanate excreted. The elimination patterns of thiocyanate in male and female rats showed no significant differences. The results suggest that a substrate saturation phenomenon is not operative with cyanide metabolism at the dosage level of potassium cyanide employed in this study. This is contrary to a previously published study which reported that the urinary excretion of thiocyanate decreased after chronic potassium cyanide administration.

Animals↗
PubMed1976

In vitro adsorption of various pharmaceutical to montmorillonite.

Dissolution and dialysis studies showed that cationic drugs and certain nonionic drugs bind strongly to montmorillonite clay. The quantity of drug bound by one unit of clay varied considerably. Anionic drugs were weakly bound, and less bioavailabilty problems would be anticipated with these medicinals. The mechanism of binding of cationic drugs to montmorillonite was proposed as a two-step process: a cation-exchange reaction followed by strong surface chemisorption.

Adsorption↗
PubMed1975

Stabilizing effect of inorganic phosphate salts on antibiotic-steroid ophthalmic preparations.

Drocinonide phosphate potassium forms an insoluble complex with neomycin sulfate in aqueous solution. Dibasic sodium phosphate can be employed in an ophthalmic formulation to prevent the formation of this precipitate without affecting the stability of the steroid or the bioactivity of the antibiotic. Other phosphate steroid salts behaved in a like manner.

Chemistry, Pharmaceutical↗
PubMed1975

Influence of monovalent and divalent electrolytes on sorption of neomycin sulfate to attapulgite and montmorillonite clays.

Langmuir isotherms for the adsorption of neomycin sulfate to clays such as attapulgite, bentonite, and magnesium aluminum silicate were constructed. Monovalent and divalent cations were investigated for their influence on the formation of neomycin-clay adsorbates and the resulting equilibrium concentration in a neomycin solution. Divalent magnesium ions were more effective in displacing the antibiotic from each clay than were monovalent sodium ions. Ions present in the GI fluid might increase the bioavailability of neomycin from such neomycin-clay adsorbates.

Adsorption↗
PubMedDate not supplied

Properties of drug-containing spherical pellets produced by a hot-melt extrusion and spheronization process.

The objectives of this study were to investigate the particle size distribution, morphology and dissolution properties of spherical pellets produced by hot-melt extrusion and spheronization and to compare the properties of hot-melt extruded pellets with beads manufactured by a traditional wet-mass extrusion and spheronization method. Spherical pellets were produced by hot-melt extrusion without the use of water or other solvents. A powder blend of theophylline, Eudragit Preparation 4135 F, microcrystalline cellulose and polyethylene glycol 8000 was hot melt-extruded and the resulting composite rod was cut into cylindrical pellets. The pellets were then spheronized in a traditional spheronizer at an elevated temperature. The same powder blend was processed using conventional wet-mass techniques. Unlike wet-mass extruded pellets, pellets prepared from hot-melt extrusion displayed both a narrow particle size distribution and controlled drug release in dissolution media less than pH 7.4. Scanning electron microscopy, X-ray diffraction and porosity measurements were employed to explain the differences in drug release rates of theophylline from pellets produced by the two processing techniques. Theophylline release from the hot-melt extruded pellets was described using the Higuchi diffusion model, and drug release rates from wet-granulated and melt-extruded pellets did not change after post-processing thermal treatment.

Biocompatible Materials↗
PubMedDate not supplied

In vitro and in vivo release properties of brilliant blue and tumour necrosis factor-alpha (TNF-alpha) from poly(D,L-lactic-co-glycolic acid) multiphase microspheres.

The dissolution properties of two model compounds, brilliant blue and tumour necrosis factor (TNF-alpha), from poly(D,L-lactic-co-glycolic acid) (PLGA) multiphase microspheres were investigated. In addition, the in vivo release of TNF-alpha from the microspheres, in mice, was studied. The microspheres were prepared by an anhydrous multiple emulsion solvent evaporation method. Multiphase microspheres containing brilliant blue exhibited a three phase release profile in vitro, and displayed a significantly lower level of dye released during the initial phase compared to conventional matrix-type microspheres. Slow release of the dye was observed during the second phase, which was followed by a disintegration of the polymer wall during the third phase of the release process. In vitro dissolution profiles of TNF-alpha were calculated by compensation for the simultaneous degradation of the protein in the dissolution medium. The initial burst release of TNF-alpha was significantly reduced with the multiphase microspheres. The three phase release profile, as seen with the dye, was not observed for the microspheres containing the TNF-alpha. The rate of release of the protein from the microspheres was determined in vivo by analysing the residual level of TNF-alpha remaining in the particles following intraperitoneal administration of the microspheres to mice. The release of the protein from the microspheres in vivo was significantly faster than predicted from the results of the in vitro studies. The absence of an initial burst release of TNF-alpha from the multiphase microspheres was reflected in a significant reduction in the plasma level of TNF-alpha when compared to the matrix-type microspheres and a solution of the protein. The controlled release property of the multiphase microspheres is expected to overcome the adverse reactions due to dose dumping that occurs following the local administration of TNF-alpha.

Animals↗
PubMedDate not supplied

Particle size and loading efficiency of poly(D,L-lactic-co-glycolic acid) multiphase microspheres containing water soluble substances prepared by the hydrous and anhydrous solvent evaporation methods.

PLGA multiphase microspheres were prepared by the multiple emulsion solvent evaporation method using acetonitrile as the polymer solvent and mineral oil as the evaporation medium. The preparation process was further developed in the present study to reduce the particle size and to increase the loading capacity of brilliant blue, bovine serum albumin (BSA) and tumour necrosis factor-alpha (TNF-alpha) which were used as water soluble model drug substances. Sorbitan sesqui-oleate (SO-15EX), present at the 1% w/w level in the evaporation medium, prevented agglomeration of the microspheres containing a solid-in-oil (S/O) suspensions as the core phase. This S/O suspension core provided significantly higher loading efficiency of the proteins to the W/O emulsion core. The W/O emulsion system resulted in agglomeration of the protein-loaded microspheres and the loading efficiency decreased significantly. When brilliant blue was included as the model compound, the loading efficiencies were not influenced by the core type. Heavy mineral oil was employed to stabilize the dispersed unhardened microspheres rather than light mineral oil that was reported previously. This anhydrous emulsion system employing the S/O suspension core and containing a dispersion of TNF-alpha enabled the encapsulation of this protein without loss of activity. It was concluded that the anhydrous emulsion system is a suitable approach to prepare multiple microspheres as an alternative to the W/O emulsion system, especially when solvent sensitive proteins are incorporated into the microspheres.

Chemistry, Pharmaceutical↗
PubMedDate not supplied

Effect of formulation factors on the matrix pH of nylon microcapsules.

The application of nylon microencapsulation as a drug delivery system inherently demands that the microencapsulated matrix should not cause degradation of the encapsulated drug. The presence of alkaline hexamethylenediamine (HMD) in the microcapsule core will affect the final pH of the microcapsules and may influence the stability of some drugs. To follow the pH within the microcapsule core during manufacture, pH indicators were encapsulated. The final pH was found to depend on the formulation used and could be controlled by the addition of acid. Several other variables affecting the nylon wall formation were examined to determine optimum processing conditions. Increased agitation produced a decrease in microcapsule size. This cause an increase in nylon weight recovered. The increased recovery of nylon was due in part to nylon formation over a larger surface area. Varying the amounts of HMD and sebacyl chloride (SC) used also affected the total weight of nylon formed. In general, more nylon is recovered as the level of each reactant increases. However, the molar ratio of HMD:SC determined the total amount of nylon formed when SC was present in excess.

Alginates↗