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Biomedical subjects

J W McGinity

Publications and source records attributed to J W McGinity.

At least 37 records · Page 2Linked to original sources
PubMed1997

Enhancement of brain p0(2) during cardiopulmonary bypass using a hyperosmolar oxygen carrying solution.

During the past decade a new syndrome has been recognized: cerebral hypoxia secondary to cardiopulmonary bypass, resulting in impairment of cognitive memory. The incidence of the syndrome appears to be no less that 30% in patients over 65 years of age undergoing cardiac surgery. There are several factors contributing to hypoxia produced by cardiopulmonary bypass. One of these factors is crystalloid pump prime and replacement solutions devoid of (1) oxygen carrying capacity and (2) devoid of protein and its colloid osmotic pressure. This shortcoming of cardiopulmonary crystalloid solutions is partially responsible for two of the three major pathologic effects of cardiopulmonary bypass: (1) hypoxia (2) interstitial fluid accumulation (anasarca, water-logging, edema). This report describes an oxygen carrying hyperosmolar solution which enhances brain p0(2) and diminishes interstitial fluid accumulation. This blood substitute consists of perfluorcarbons and saccharides, but could consist of a hemoglobin variant plus hyperosmolar ingredients other than saccharides. The advantage of a perfluorochemical is its ability to access small channels and to be centrifuged off the patient post-operatively with a cell saver. The advantage of saccharides is that they can be metabolized by the patient for energy, and they produce a moderate diuresis coming off bypass.

Animals↗
PubMed1996

Mechanical properties of single pellets containing acrylic polymers.

Three aqueous-based acrylic latex dispersions, Eudragit L 30 D, NE 30 D, and RS 30 D, were incorporated as granulating binders into a powder blend of microcrystalline cellulose and anhydrous lactose by wet massing. Spheronized pellets were prepared by extrusion-spheronization and the mechanical properties of single pellets, including the tensile strength at break and the Young's modulus were determined from the stress-strain profiles using a Chatillon TCD-200 tension/compression digital test gauge. The influence of particle size and plasticizer on the mechanical properties of pellets containing Eudragit RS 30 D was investigated. All bead formulations deformed by brittle fracture under a diametral compression force. The mechanical strength was found to be influenced by the adhesive strength between the polymers and the powder particles instead of the cohesive strength of each polymer. The Young's modulus and the tensile strength were also significantly influenced by the type and concentration of polymer, the presence of plasticizer, and the particle size of the beads. The results were related to the properties of the polymers and the fracture mechanisms of the beads. Furthermore, the polymer type and the incorporation of plasticizer influenced the susceptibility of the moistened extruded granules to the shearing forces during the spheronization process, which influenced the surface morphological properties of the pellets.

Acrylates↗
PubMed1996

Influence of tablet hardness and hydrophobicity on the adhesive properties of an acrylic resin copolymer.

The adhesive properties--including the force of adhesion, elongation at adhesive failure, the modulus of adhesion, and the adhesive toughness--of an acrylic resin copolymer were determined using the butt adhesion technique. Flat-faced tablets containing up to 30% hydrogenated castor oil were coated with an aqueous dispersion of Eudragit L30D-55. Using data obtained from a Chatillon digital force gauge attached to a motorized test stand, force-deflection profiles, similar to stress-strain curves generated in the tensile testing of free films, were constructed. The surface characteristics of the tablets significantly influenced polymer-substrate interaction. The force of adhesion, the elongation at adhesive failure, and the adhesive toughness decreased as the surface of the tablet became more hydrophobic through the addition of wax to the tablet formulation. Lower adhesive properties were found with increasing tablet hardness, due to a decrease in the effective area of contact between the film coating and the tablet surface. Increased polymer loading resulted in stronger adhesion, indicating a relationship between the mechanical and adhesive properties of the polymer. The present study demonstrated that the area under the force-deflection profile in conjunction with the force of adhesion was more representative of the adhesive properties of the polymer.

Acrylic Resins↗
PubMed1994

Properties of free films prepared from aqueous polymers by a spraying technique.

A spray method for the preparation of free films from aqueous polymeric dispersions was investigated. Free films were prepared from aqueous dispersions of methacrylic acid-ethyl methacrylate copolymer (Eudragit L 30D), hydroxypropyl methylcellulose acetate succinate (HPMCAS), cellulose acetate phthalate (CAP), and ethyl cellulose (EC) by a spray method and a cast method, and their mechanical properties and reproducibility were investigated. Uniform films were obtained from the dispersions of Eudragit L 30D, HPMCAS, and EC by the spray method, but films could not be formed by spraying the CAP dispersion. The tensile strength, elongation, and elastic modulus of the sprayed Eudragit L 30D films were similar to the properties of the cast films, and good reproducibility was obtained from both methods. Marked within-run variation in the mechanical properties was observed for the cast HPMCAS and CAP films, which could be due to a settling of the solid particles during the drying step. The variation in the mechanical properties of the sprayed HPMCAS films was lower and the tensile strength significantly higher than that of the cast films. There were also significant differences in tensile strength and elongation of EC films between products of the two methods. The results indicated that the spray method used to prepare the free films from aqueous polymeric dispersions provided uniform films with consistent and reproducible properties.

Acrylic Resins↗
PubMed1993

Dissolution, stability, and morphological properties of conventional and multiphase poly(DL-lactic-co-glycolic acid) microspheres containing water-soluble compounds.

Multiphase microspheres of poly(DL-lactic-co-glycolic acid) (PLGA) containing water-soluble compounds were prepared by a multiple-emulsion solvent evaporation technique. These compounds were dissolved in the aqueous phase of a W/O emulsion with soybean oil as the oil phase. This emulsion was dispersed throughout the matrix of the microsphere. The morphological properties of the multiphase microspheres during in vitro dissolution studies were compared to those of conventional microspheres prepared from the same polymer. Drug release from the multiphase microspheres was characterized by an initial uniform release for the first 20 days followed by a more rapid phase of drug release. Chlorpheniramine maleate (CPM) and brilliant blue (BB) were the soluble model compounds investigated. The release rates of these agents from the multiphase microspheres were independent of the drug content in the microspheres. The release profiles from the conventional microspheres showed a lag time of 10 and 16 days for the CPM and BB, respectively. The dissolution rate of the model soluble compounds from the conventional microspheres increased as the loading in the microspheres increased. No differences in the degradation rate of the PLGA from the multiphase and the conventional microspheres were seen during the dissolution studies.

Acetonitriles↗
PubMed1993

The influence of thermal treatment on the physical-mechanical and dissolution properties of tablets containing poly(DL-lactic acid).

Five molecular weight grades of poly(DL-lactic acid) (PLA) were incorporated as organic and aqueous pseudolatex binders into matrix tablet formulations containing microcrystalline cellulose and the model drug theophylline. The tablets were thermally treated to temperatures above and below the glass transition temperature (Tg) of the PLA. The results of the dissolution studies showed that thermally treating the tablets to temperatures above the Tg of the PLA significantly retarded the matrix drug release compared to tablets which were not thermally treated. The retardation in drug release could be attributed to a stronger compact and a more efficient redistribution of polymer throughout the tablet matrix, based on fundamental principles of annealing. In addition, results from tablet index testing supported the dissolution results. The bonding index of the compact formulations increased after thermal treatment above the Tg of the PLA. Gel permeation chromatography and differential scanning calorimetry studies demonstrated that thermal treatment had no significant effect on the molecular weight and the glass transition temperature of (PLA) alone and in combination with other components of the tablet formulation.

Calorimetry, Differential Scanning↗
PubMed1992

Relationship of film properties to drug release from monolithic films containing adjuvants.

The rate of drug release from a polymeric matrix system was influenced by the physical and chemical properties of the monolithic films. The model drugs, salicylic acid and chlorpheniramine maleate, and two poly(methyl methacrylate) copolymers of different permeabilities (Eudragit RL and Eudragit RS), with and without additional adjuvants, were used to form monolithic matrix films for controlled drug release. Adjuvants, including polyethylene glycols (PEG 400 and PEG 8000) and poly(vinylpyrrolidones) (PVP-K15 and PVP-K90), were incorporated into films of Eudragit RL PM and Eudragit RS PM. The moisture permeation constant, glass transition temperature (Tg), tensile strength, and drug release profiles were determined for each acrylic resin slab to correlate the physicochemical and physicomechanical film properties to observed drug release. Faster rates of drug diffusion were observed with the addition of PEG 400 to the films, because of its plasticizing effect and the resultant increased moisture permeability of the matrix. An exception existed with the Eudragit RL PM film containing salicylic acid where drug-polymer interactions inhibited drug diffusion. The small changes in moisture permeability, Tg, and tensile strength observed with incorporation of the PVPs had an insignificant influence on the dissolution results for salicylic acid from Eudragit RS PM films. Increases in the tensile strength and Tg after addition of PVP to the Eudragit RS PM matrix support the observed decreased rate of diffusion for chlorpheniramine maleate. The pores formed by migration of the hydrophilic adjuvants from the films altered the diffusion kinetics of the matrix, compared with that of the nonporous polymer, when only the antihistamine was present.

Acrylic Resins↗
PubMed1992

The influence of polymer glass transition temperature and molecular weight on drug release from tablets containing poly(DL-lactic acid).

Five molecular weight grades of poly(DL-lactic acid) were characterized using gel permeation chromatography, differential scanning calorimetry, and viscometry to determine the effect of molecular weight on the glass transition temperature and the intrinsic viscosity. In addition, dynamic mechanical thermal analysis was used to assess the dynamic storage modulus and the damping factor of the polymer samples by detecting motional and structural transitions over a wide temperature range. Significant relationships were found between the molecular weight and these polymer properties. The five grades of poly(DL-lactic acid) were also incorporated as binders into matrix tablet formulations containing the model drug theophylline and microcrystalline cellulose. Dissolution studies showed significant correlations between the properties of the polymer and the matrix release profiles of the tablets. The release of theophylline slowed down progressively as the polymer molecular weight increased. The differences in release became less significant and reached a limiting asymptotic value as the molecular weight increased to 138,000. Further, tablet index testing was utilized to determine the compaction properties of the polymer granulations. Although there was no correlation with the molecular weight of PLA, brittle fracture index testing indicated very low brittleness for all granulations tested. However, bonding index determinations correlated very well with both the physical-mechanical properties of the polymer and drug release profiles.

Biomechanical Phenomena↗
PubMed1992

Biodegradable pseudolatexes: the chemical stability of poly(D,L-lactide) and poly(epsilon-caprolactone) nanoparticles in aqueous media.

Pseudolatexes of the biodegradable polyesters poly(D,L-lactide) (PLA) and poly(epsilon-caprolactone) (PCL) have been developed as potential aqueous coatings for sustained release. Since PLA and PCL are known to hydrolyze, the influence of the surfactant system, temperature, pH, and particle size on the chemical stability of the polymers as aqueous colloidal dispersions was investigated. Pseudolatexes of PLA and PCL formulated with a nonionic surfactant system were the most stable. When these dispersions were stored in unbuffered media for 350 days at 5 degrees C, only small changes in the weight-average molecular weights (Mw) of the polymers were observed. At 37 degrees C there was rapid degradation of both polymers in the dispersions. Arrhenius plots for the degradation of PLA and PCL resulted in a linear relationship for PCL. The nonlinear relationship for PLA was attributed to the polymer being in two different physical states within the 5 to 37 degrees C range which was used for the Arrhenius plots. PCL was in the rubbery state at all temperatures studied. Storage of the pseudolatexes in pH 1.65 buffer at 37 degrees C catalyzed the rates of degradation of both PLA and PCL. However, refrigeration of the pseudolatexes stabilized the polymers even at pH 1.65 for up to 4 months. Particle size had an insignificant effect on PLA and PCL stability in pseudolatexes prepared with either a nonionic or an anionic surfactant system.

Calorimetry, Differential Scanning↗
PubMed1990

Physical and chemical factors influencing the release of drugs from acrylic resin films.

An investigation was conducted to evaluate the factors influencing the release of salicylic acid and chlorpheniramine maleate from polymethacrylate amino-ester copolymer films (Eudragits RL PM and RS PM). Differential scanning calorimetry was performed on the films to study the solubility of drug in the polymer and to determine the effect of added drug on the thermal properties of the film. Incorporation of drug into the polymers decreased the glass transition temperature of the polymers. Dissolution of drug from monolithic slabs was followed as a function of temperature, drug concentration in the films, and ionic strength of the release media. In addition, adsorption studies were conducted with each drug:polymer combination to help explain release results and further characterize the drug:polymer interactions that occurred. The rate of drug release increased with increasing temperature. Adsorption of salicylic acid by the polymers was believed to influence the drug release profiles observed for different drug loadings and ionic strengths. Eudragit RL was found to adsorb salicylic acid to a greater extent than the Eudragit RS. Chlorpheniramine maleate was not found to be adsorbed by either polymer.

Acrylates↗
PubMed1989

Compaction properties of microcrystalline cellulose and sodium sulfathiazole in combination with talc or magnesium stearate.

The dynamic indentation hardness, tensile strength, bonding index, and brittle fracture index were employed to investigate the compaction properties of a plastic excipient, microcrystalline cellulose, and a brittle drug, sodium sulfathiazole, in combination with different levels of either magnesium stearate or talc. These parameters were also used to quantitate properties of various combinations of microcrystalline cellulose and sodium sulfathiazole in order to illustrate the effects of combining a plastic excipient and a brittle drug. It was shown that the tensile strength, indentation hardness, bonding index, and brittle fracture index for compacts composed of microcrystalline cellulose in combination with either talc or magnesium stearate generally decreased as the amount of talc or magnesium stearate was increased over the concentration range of 0 to 9%. Similar results were observed for admixtures of sodium sulfathiazole in combination with either talc or magnesium stearate. It was also demonstrated that the tensile strength, indentation hardness, and bonding index increased, and the brittle fracture index decreased, as the percent of microcrystalline cellulose was increased in a binary mixture of sodium sulfathiazole and microcrystalline cellulose.

Cellulose↗
PubMed1987

The preparation and evaluation of drug-containing poly(dl-lactide) microspheres formed by the solvent evaporation method.

Several compounds such as caffeine, diazepam, hydrocortisone, progesterone, quinidine, quinidine hydrochloride, quinidine sulfate, and theophylline were evaluated for incorporation into poly(dl-lactide) (PLA) microspheres using the solvent evaporation technique. The process is generally limited to the entrapment of water-insoluble drugs. Adjustment of the pH of the aqueous phase to minimize drug solubility resulted in increased drug contents within the microspheres in the case of ionizable drugs. The release profile of quinidine from the microspheres was characterized by three different release phases, a lag time with no drug release, a burst effect of rapid drug release within a short period of time, and a slow release phase, respectively. The structure of the microsphere surface layer, which was a function of the pH of the aqueous phase at preparation, strongly influenced the rate and amount of drug released. Thermal analysis of quinidine-loaded microspheres revealed three thermal events, corresponding to the glass transition temperature of the polymer and to the recrystallization and melting of quinidine.

Drug Carriers↗
PubMed1984

Crystallinity and dissolution rate of tolbutamide solid dispersions prepared by the melt method.

The influence of cooling rate of solid dispersions prepared by the melt method was studied by X-ray diffraction and scanning electron microscopy. Tolbutamide was the model drug investigated, and the carriers included urea and polyethylene glycol 6000. Slow-cooled urea dispersions of tolbutamide demonstrated a complete lack of crystallinity, suggesting the formation of an amorphous material. The rapidly cooled dispersion showed peaks for urea and an absence of drug in the X-ray pattern, suggesting that a true molecular dispersion was formed. The X-ray patterns of rapid- and slow-cooled dispersions of tolbutamide and polyethylene glycol 6000 demonstrated that a physical mixture of drug and carrier resulted from both methods of dispersion preparation.

Chemical Phenomena↗
PubMed1982

A new subcutaneously-implantable reservoir for sustained release of nicotine in the rat.

A subcutaneously-implantable reservoir for the sustained release of nicotine is described. The device, dubbed INR for Implantable Nicotine Reservoir, is a small glass cup sealed with Silastic polymer. It releases 3.4 mg of nicotine per 24 hours. When implanted into moderately-sized female Sprague-Dawley rats it produces blood nicotine levels of 400-500 ng/ml which remain relatively stable over at least 18 days. INRs are nontoxic, reproducible, inexpensive, and adaptable for pharmacological and toxicological studies in rats and other small animals.

Animals↗
PubMed1981

Influences of matrixes on nylon-encapsulated pharmaceuticals.

The preparation and properties of nylon microcapsules containing three different matrixes (formalized gelatin, calcium alginate, and calcium sulfate) are described. Microcapsules containing each matrix were dense and free flowing and could be made of very small diameter by controlling the stirring speed during nylon formation. The preparation of microcapsules containing calcium alginate employed freeze-drying procedures. Lyophilization was not necessary with the formalized gelatin and calcium sulfate systems. Various representative drugs (anionic, cationic, nonionic, quaternary, and amphoteric compounds) were used in the formulation studies. The effects of pH, matrix, and encapsulated species on retention of drug in the microcapsules are described. In addition, the surface morphology of the microcapsules was examined using scanning electron microscopy.

Capsules↗
PubMed1980

Polydimethylsiloxane pellets for sustained delivery of morphine in mice.

A new dosage form was designed whereby a polymeric silicone elastomer provided sustained delivery of morphine to mice over 11 days. These pellets, which can be made easily and inexpensively with a standard tablet mold, gradually released morphine sulfate into the implanted mice. Maximal morphine-induced physical dependence, measured by jumping during naloxone-induced withdrawal, was observed 3--5 days after implantation. At this time, slightly less than 50% of the morphine sulfate had been released. Drug release continued through Day 11 and was accompanied by a physical dependence of decreased magnitude compared to that observed on Day 3 or 5.

Animals↗