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Biomedical subjects

J W McGinity

Publications and source records attributed to J W McGinity.

At least 19 recordsLinked to original sources
PubMed2001

Bioadhesive properties of hydroxypropylcellulose topical films produced by hot-melt extrusion.

The objective of this study was to investigate the in vivo bioadhesive properties of hydroxypropylcellulose (HPC) films containing seven polymer additives on the epidermis of 12 human subjects, including two ethnic sub-groups. HPC films containing polyethylene glycol (PEG 3350) alone, Vitamin E TPGS (TPGS) 5%, sodium starch glycolate 5%, Eudragit E-100 5%, carbomer 974P and 971P 5%, and polycarbophil 5%, all with and without plasticizer, were prepared by hot-melt extrusion utilizing a Randcastle Microtruder (Model #RCP-0750). Bioadhesion testing was performed using a Chatillon digital force gauge DFGS50 attached to a Chatillon TCD-200 motorized test stand to determine force of adhesion (FA), elongation at adhesive failure (EAF), and modulus of adhesion (MA) for the 12 films tested. In vivo, the TPGS-incorporated film exhibited a two-fold increase in FA when compared to the control film containing the PEG 3350 5%. The carbomer 971P and polycarbophil containing films were determined to have the highest FA and EAF, and the lowest MA of all films tested. The film containing carbomer 971P had a higher FA than the film containing 974P. In addition, films in one ethnic sub-group exhibited higher FA and EAF than the other. Force--deflection profiles obtained from these experiments indicate that the force of adhesion, elongation at adhesive failure and modulus of adhesion are a function of the polymer additive in the HPC extruded films. The incorporation of carbomer 971P and a polycarbophil into HPC films increased bioadhesion significantly when compared to the film containing HPC and PEG 3350. Differences in FA and EAF were discovered between two ethnic sub-groups tested.

Adhesives↗
PubMed2001

Properties of lipophilic matrix tablets containing phenylpropanolamine hydrochloride prepared by hot-melt extrusion.

The objective of the present study was to investigate the influence of formulation factors on the physical properties of hot-melt extruded granules and compressed tablets containing wax as a thermal binder/retarding agent, and to compare the properties of granules and tablets with those prepared by a high-shear melt granulation (MG) method. Powder blends containing phenylpropanolamine hydrochloride, Precirol and various excipients were extruded in a single-screw extruder at open-end discharge conditions. The extrudates were then passed through a 14-mesh screen to form granules. The extrusion conditions and the optimum amount of wax to function as the thermal binder were dependent on the properties of the filler excipients. At the same wax level, drug release from tablets decreased in the order of using microcrystalline cellulose (MCC), lactose and Emcompress as the filler excipient. The observed differences in the dissolution properties of the tablets were due to the differences in the solubility, swellability and density of the filler excipients. Replacing Precirol with Sterotex K, a higher melting point wax, resulted in slightly increased dissolution rates, when the extrusion was performed at the same temperature conditions. Hot-melt extruded granules were observed to be less spherical than high-shear melt granules and showed lower values of bulk/tap densities. However, tablets containing MCC or lactose granules prepared by hot-melt extrusion (HME) exhibited higher hardness values. Slower drug release rates were found for tablets containing MCC by HME compared with MG. Analysis of the hot-melt extruded granules showed better drug content uniformity among granules of different size ranges compared with high-shear melt granules, resulting in a more reproducible drug release from the corresponding tablets.

Adrenergic alpha-Agonists↗
PubMed2001

Influence of film additives on stabilizing drug release rates from pellets coated with acrylic polymers.

The objective of this study was to investigate the influence of talc and triethyl citrate (TEC) on stabilizing the drug release rates following curing and storage at elevated temperature of pellets coated with an aqueous acrylic polymeric dispersion. Core pellets containing anhydrous theophylline (20%), microcrystalline cellulose, and polyvinylpyrrolidone were prepared by extrusion-spheronization. The aqueous dispersions were prepared by adding up to 30% TEC as a plasticizer and talc up to 200% as an antiadherent to a mixture of Eudragit RS 30D/RL 30D (95:5). The theophylline pellets were coated in a fluidized-bed coating unit and then cured at elevated temperatures. Theophylline pellets were successfully coated with the Eudragit dispersions that contained up to 200% talc, based on the dry polymer weight, and the coating efficiency was greater than 93%. Our results demonstrated that the polymer, which was plasticized by TEC, was able to function as a film-forming agent for dispersions containing high levels of talc. No sticking of the coated pellets was observed during the coating process or during the curing or equilibrating phase, even with high levels of TEC in the film. The dissolution rate of theophylline from the coated pellets was delayed when the film coating dispersion contained high levels of talc. Additionally, the stability of the drug release profiles from the coated pellets after storage was significantly improved. Furthermore, a modified dissolution testing used to simulate mechanical stresses that may be encountered in vivo showed the film coated pellets would have sufficient strength. The results of this study demonstrated that high levels of film additives in the acrylic dispersion contributed to the stabilization of the drug release rates as well as the reproducibility of the coating process.

Acrylic Resins↗
PubMed2001

Properties of tablets containing granulations of ibuprofen and an acrylic copolymer prepared by thermal processes.

The objective of this study was to investigate the properties of tablets containing granulations of ibuprofen (Ibu) and Ammonio Methacrylate Copolymer, Type B (Eudragit RS PO) prepared by hot-melt processing. Tablets were compressed from granules prepared by hot-melt granulation (HMG) or direct compression (DC). For the hot-melt extrusion (HME) process, tablets were prepared by cutting the extrudate, manually. The physicochemical properties of tablets were investigated using thermal analysis, powder X-ray diffraction analysis, tablet hardness, and drug dissolution. The effect of thermal treatment of tablets on the dissolution characteristics of Ibu was also investigated. The results demonstrated that the Ibu lowered the glass transition temperature (Tg) of the Eudragit RS PO and the softened polymer functioned as a thermal binder in the granulation. Ibu was demonstrated to be an effective plasticizer for Eudragit RS PO in the thermal processes. The efficiency of the granulation process increased with increasing levels of Eudragit RS PO in the powder blend. Higher levels of Eudragit RS PO in the tablets prepared by HMG or HME resulted in a decrease in the dissolution rate of the Ibu. An increase in the amount of Ibu in the tablets prepared by HMG or DC led to a decrease in the initial dissolution rate of the Ibu. Following the thermal treatment of the Ibu tablets prepared by HMG, the dissolution rate was significantly decreased due to structural changes in the tablets that resulted from the fusion and coalescence of plasticized polymer particles, causing a reduction in tablet porosity. The Ibu tablets prepared by HME demonstrated minimal changes in their release properties following thermal treatment even at temperatures higher than the Tg of the polymer. HME was shown to be a novel method to prepare matrix tablets and stable dissolution properties were obtained when tablets were stored at 40 degrees C for 30 days.

Acrylic Resins↗
PubMed2001

Influence of chlorpheniramine maleate on topical hydroxypropylcellulose films produced by hot-melt extrusion.

The objective of this investigation is to study the influence of chlorpheniramine maleate (CPM) on the chemical and physical-mechanical properties of hydroxypropylcellulose (HPC) hot-melt extruded films without the use of a traditional plasticizer HPC films containing CPM in concentrations of 1, 5, and 10 wt% were prepared by hot-melt extrusion utilizing a Randcastle Microtruder (Model #RCP-0750) with a 6-in. flex-film die. The physical-mechanical properties including tensile strength and percent elongation were determined on an Instron according to the ASTM standards. Glass transition temperatures and thermal analysis of the extruded films were determined utilizing a DSC 2920 Modulated DSC and Thermal Analyst 2000 software. The crystalline properties of the drug, polymer, and extruded films were studied via wide angle X-ray diffraction (XRD) using a Philips Vertical Scanning Diffractometer (Type 42273, Philips Electronic Instrument, Mount Vernon, NY). Gel permeation chromatography was used to study the stability of the polymer matrix as a function of different concentrations of CPM and processing conditions. CPM functioned as an effective plasticizer, increasing percent elongation and decreasing tensile strength in a concentration dependent manner All three concentrations of extruded films exhibited a 10- to 12-fold decrease in tensile strength in contrast to a fourfold increase in percent elongation when testing was performed perpendicular to flow vs. in the direction of flow. The drug was also shown by XRD and DSC data to be in solution in the HPC matrix within the films up to the 10% level. In addition, CPM functioned as a processing aid in the extrusion of hot-melt films, stabilizing the weight-average molecular weight of HPC and allowing for film processing at lower temperatures. CPM could potentially be a candidate antihistamine for transdermal or transmucosal applications in film devices prepared by hot-melt extrusion technology.

Administration, Topical↗
PubMed2000

Influence of vitamin E TPGS on the properties of hydrophilic films produced by hot-melt extrusion.

Films containing hydroxypropylcellulose (HPC) and polyethylene oxide (PEO) were prepared using a Randcastle extruder (Model 750) with and without Vitamin E TPGS (TPGS, D-alpha-tocopheryl polyethylene glycol 1000 succinate) as an additive. Conventional plasticizers including polyethylene glycol 400 (PEG 400), triethyl citrate (TEC), and acetyltributyl citrate (ATBC) were also incorporated into films containing a 50:50 blend of HPC and PEO. The physical-mechanical properties including tensile strength (TS) and percent elongation (%E) were determined on an Instron according to the ASTM standards. Glass transition temperatures (T(g)) of the extruded films were determined utilizing a DSC 2920 Modulated differential scanning calorimeter and THERMAL ANALYST 2000 software. Gel permeation chromatography was used to study the stability of the polymer films under the processing conditions. The addition of 1, 3, and 5% Vitamin E TPGS, respectively, decreased the glass transition temperature of the extruded films containing either a 50:50 or 80:20 ratio of HPC to PEO in an almost linear fashion. In addition, the presence of 3% Vitamin E TPGS lowered the T(g) over 11 degrees C when compared with the HPC/PEO 50:50 blend film without TPGS, thus functioning as a plasticizer. The tensile strength decreased with increasing concentrations of TPGS, and the %E increased over 3-fold when compared with the HPC/PEO film that contained no additives. The film containing 3% Vitamin E TPGS had a similar tensile strength to that of the films containing 3% PEG 400, and a 3-fold increase in percent elongation when compared with the films containing 3% TEC and 3% ATBC. In addition, the Vitamin E TPGS facilitated the processing of the HPC/PEO films by decreasing the barrel pressure, drive amps, and torque of the extruder equipment.

Administration, Cutaneous↗
PubMed2000

Physical-mechanical, moisture absorption and bioadhesive properties of hydroxypropylcellulose hot-melt extruded films.

The objective of this study was to investigate the moisture absorption, physical-mechanical and bioadhesive properties of hot-melt extruded hydroxypropylcellulose (HPC) films containing polymer additives. These additives included polyethylene glycol (PEG) 5%, polycarbophil 5%, carbomer 5%, Eudragit E-100 5%, and sodium starch glycolate (SSG) 5%. Relative humidity (RH) and temperature parameters of the films studied included 25 degree C at 0, 50, 80 and 100% RH, and 40 degrees C at 0 and 100% RH, stored for 2 weeks. Tensile strength and percent elongation were determined on an Instron according to the ASTM standards. The bioadhesive properties of the HPC/PEG 3350 5% film and the polycarbophil 5% containing films, with and without PEG, were investigated in vivo on the human epidermis. Although all films studied exhibited an increase in percent water content as the percent RH increased, the SSG containing film exhibited an almost three-fold increase in percent water content compared to that of the HPC/PEG film. The temperature storage condition of 40 degrees C/100% RH (versus 25 degrees C/100% RH) increased the percent water content of the SSG containing film. Percent elongation was highest for films containing polycarbophil 5% (without PEG). In addition, the HPC film containing polycarbophil 5% exhibited a greater force of adhesion and elongation at adhesive failure in vivo, and a lower modulus of adhesion when compared to the HPC/PEG film. A novel approach to determine bioadhesion of films to the human epidermis is presented.

Acrylic Resins↗
PubMed2000

Influence of relative humidity on the mechanical and drug release properties of theophylline pellets coated with an acrylic polymer containing methylparaben as a non-traditional plasticizer.

The purpose of this study was to investigate the influence of relative humidity (RH) on the mechanical and dissolution properties of theophylline pellets coated with Eudragit((R)) RS 30 D/RL 30 D containing methylparaben (MP) as a non-traditional plasticizer. The coated beads were stored at 23 degrees C and at different relative humidities (0, 29, 51, 75 and 84% RH). The effect of storage conditions on the rate of drug release from coated beads was determined in pH 7.4 phosphate buffer solution. The mechanical properties, including tensile strength and Young's modulus, of individual beads were determined by a diametral compression method with a Chatillon((R)) tension/compression apparatus. The morphology of the intact and fractured beads was investigated using scanning electron microscopy (SEM). The moisture content of the polymeric films was determined using a Karl Fischer coulometric moisture analyzer. The results from the mechanical studies demonstrated that an increase in the relative humidity resulted in a decrease in the tensile strength and Young's modulus of the coated beads. SEM photographs showed that coated beads stored at 0% RH exhibited brittle fracture failure. The coated beads stored at 84% RH showed ductile behavior, which was attributed to the hydroplasticization effect on the acrylic polymer due to the uptake of moisture. The moisture content in the films was also shown to influence the rate of drug release from Eudragit((R)) RS 30 D/RL 30 D coated beads containing MP as the plasticizer. The change in release profiles could be minimized when the relative humidity was reduced to zero. The dissolution rate of theophylline from the coated beads decreased when stored at high relative humidities. This trend was reversed when the coated beads that were stored at 84% RH for 5 weeks, were then equilibrated at 0% RH.

Humidity↗
PubMed2000

Properties of hot-melt extruded theophylline tablets containing poly(vinyl acetate).

The objectives of this study were to investigate the properties of poly(vinyl acetate) (PVAc) as a retardant polymer and to study the drug release mechanism of theophylline from matrix tablets prepared by hot-melt extrusion. A physical mixture of drug, polymer, and drug release modifiers was fed into the equipment and heated inside the barrel of the extruder. The cylindrical extrudates were either cut into tablets or ground into granules and compressed with other excipients into tablets. Due to the low glass transition temperature of the PVAc, the melt extrusion process was conducted at approximately 70 degrees C. Theophylline was used as the model drug in this study. Theophylline was present in the extrudate in its crystalline form and was released from the tablets by diffusion. The Higuchi diffusion model and percolation theories were applied to the dissolution data to explain the drug release properties of the matrix systems. The release rate was shown to be dependent on the granule size, drug particle size, and drug loading in the tablets. Water-soluble polymers were demonstrated to be efficient release rate modifiers for this system.

Bronchodilator Agents↗
PubMed1999

Non-traditional plasticization of polymeric films.

The objective of this study was to investigate the influence of methylparaben, ibuprofen, chlorpheniramine maleate and theophylline on the thermal and mechanical properties of polymeric films of Eudragit RS 30 D. The effects of methylparaben and ibuprofen in the film coating on the rate of drug release from Eudragit RS 30 D coated beads were also studied. The physical and mechanical properties of the cast films and coated beads were investigated using thermal analysis, tensile testing, X-ray diffraction analysis and dissolution testing. The results demonstrated that the glass transition temperature of the Eudragit RS 30 D decreased with increasing levels of methylparaben, ibuprofen and chlorpheniramine maleate in the film. Theophylline exerted no influence on the thermal properties of the polymer. The higher levels of the ibuprofen and methylparaben incorporated into the film resulted in a decrease in the tensile strength of the film. The decrease in Young's modulus of Eudragit RS 30 D coated beads was attributed to an increase in the flexibility of the polymeric films when the level of methylparaben or ibuprofen in the polymeric dispersion was increased. The dissolution data demonstrated that the rate of release of the ibuprofen from coated beads was decreased by increasing the amount of ibuprofen and methylparaben in the polymeric film coating.

Chlorpheniramine↗
PubMed1999

Adhesion of polymeric films to pharmaceutical solids.

The two major forces influencing polymer adhesion include the strength of the interfacial bonds between the polymeric film and the surface of the solid and the internal stresses within the film coating. While good adhesion between the polymer and the substrate is desirable for pharmaceutical products, the small size of the dosage form and the non-uniform surface roughness have created difficulties in assessing polymer adhesion. In this review, the experimental devices and procedures used to quantitate polymer adhesion are addressed. The affects of the physical and chemical properties of the substrate, including surface roughness and tablet hydrophobicity, on adhesion of a polymer to either tablets or capsules are discussed. The influence of the plasticizers, pigments, and solvents in film coating formulations on polymer adhesion, and the effects of aging of the coated solids on adhesion of polymers to tablets and capsules are also discussed.

Adhesiveness↗
PubMed1999

Aqueous ethyl cellulose dispersion containing plasticizers of different water solubility and hydroxypropyl methyl-cellulose as coating material for diffusion pellets II: properties of sprayed films.

This study investigates the properties of sprayed films prepared from aqueous ethyl cellulose dispersions (ECD) containing hydroxypropyl methylcellulose (HPMC) and plasticizers of different water solubility in order to clarify the drug release mechanisms of pellets coated with the respective material. It is of special interest to measure the migration of the water soluble components as well as the physical properties of the swollen ethyl cellulose film. Swelling experiments with sprayed films in 0.1 N-HCl at 37 degrees C show that fairly water soluble plasticizers and the pore forming agent (HPMC) migrated rapidly and almost completely out of the films. The water insoluble plasticizers remain predominantly in the film and the migration rate of HPMC is reduced in a release medium of high ionic strength. The glass transition temperature (T(g)) and the softening temperature (T(s)) of these films after swelling are dependent on the water solubility of the plasticizer. The T(g) of ECD films plasticized with triethyl citrate is above the swelling temperature of 37 degrees C after migration of the plasticizer, transforming the polymer in the glassy state. In contrast, dibutyl phthalate-containing ECD films demonstrate a T(g) below the swelling temperature, leaving the polymer in the rubbery state. The mechanical properties of dry and wet films are studied as a function of the state of curing of the films and of the swelling temperature. On contact with water, a pronounced shrinkage of ECD/HPMC films plasticized with water insoluble plasticizers is observed. All these results are used to explain the different drug release mechanisms of the coated pellets and to enable the prediction and optimization of drug release-rates from coated pellets.

Algorithms↗
PubMed1999

Influence of pigment concentration and particle size on adhesion of an acrylic resin copolymer to tablet compacts.

The effects of the particle size and the concentration of pigments in aqueous polymeric dispersions on the adhesive properties of an acrylic resin copolymer were investigated. Aqueous polymeric dispersions containing up to 20% (v/v) pigment were coated onto hydrophilic and hydrophobic tablet compacts, and polymer adhesion was assessed using a novel butt adhesion technique. An inverse relationship was found between the particle size of the pigment present in the aqueous polymeric dispersion and film-tablet adhesion. As the particle size of the pigment increased, the adhesive strength of the polymer to the tablet compact decreased. Increased concentrations of the opacifying agent titanium dioxide in the acrylic dispersion resulted in stronger film-tablet adhesion. No clear relationship could be established between the wettability of the tablet compact by the pigmented polymeric dispersion and the strength of film-tablet adhesion. The hydrophobicity of the tablet compact was found to affect the glass transition temperature of the polymeric film to a greater extent than the particle size, morphology, or concentration of the pigment incorporated into the acrylic dispersion.

Acrylic Resins↗
PubMed1999

Influence of plasticizers and drugs on the physical-mechanical properties of hydroxypropylcellulose films prepared by hot melt extrusion.

Hydroxypropylcellulose (HPC) films containing drugs or hydrophilic or hydrophobic plasticizers were prepared by a hot melt extrusion process. Polyethylene glycol 8000 (PEG 8000) 2%, triethyl citrate (TEC) 2%, acetyltributyl citrate (ATBC) 2%, and polyethylene glycol 400 (PEG 400) 1% were the plasticizing agents studied. In addition, either hydrocortisone (HC) 1% or chlorpheniramine maleate (CPM) 1% was incorporated into the films as a model drug. The physical-mechanical properties of the films that were investigated included tensile strength (TS), percentage elongation (%E), and Young's modulus (YM). Differential scanning calorimetry (DSC) was utilized to determine glass transition temperatures (Tg's). These parameters were studied as a function of time and temperature. The glass transition temperatures initially decreased with the inclusion of the drugs and plasticizers. However, after 6 months aging, films containing PEG 400 and HC showed a marked increase in Tg. The films containing PEG 400 showed physical-mechanical instability in all parameters studied. All extruded films exhibited a marked decrease in TS in contrast to a large increase in %E when testing was performed perpendicular to flow versus in the direction of flow. In addition, a consistent film of HPC in the absence of drugs or plasticizers could not be extruded due to the excessive stress on the equipment. Although the theoretical percentage of CPM on aging remained fairly constant over the processing temperature ranges in this study, the HC levels remaining in the extruded films during storage were a function of time and temperature.

Cellulose↗
PubMed1999

Properties of sustained-release tablets prepared by hot-melt extrusion.

The objectives of the present study were to investigate the properties of polyethylene oxide (PEO) as a drug carrier and to study the release mechanism of chlorpheniramine maleate (CPM) from matrix tablets prepared by hot-melt extrusion. During the hot-melt extrusion process, a dry powder blend of drug, polymer, and other adjuvants was fed into the extruder and melted inside the barrel of the machine. The molten mass was extruded through a rod-shaped die and then cut manually into 400-mg tablets. CPM and PEO were shown to be stable under the processing conditions. The molecular weight of the PEO, the drug loading percentage, and the inclusion of polyethylene glycol as a processing aid, were all found to influence the processing conditions and the drug release properties of the extruded tablets. Faster release of CPM from the matrix tablets was observed in acidic medium than in purified water and phosphate buffer (pH 7.4). Drug release from the matrix tablet was controlled by erosion of the PEO matrix and the diffusion of the drug through the swollen gel layer at the surface of the tablets. CPM was dispersed at the molecular level in the PEO matrix at low drug loading level and recrystallization of CPM was observed at high drug loading levels. Hot-melt extrusion was demonstrated to be a viable novel method to prepare sustained-release tablets. PEO was shown to be a suitable polymeric carrier for this process.

Chlorpheniramine↗
PubMed1998

Influence of processing on the stability and release properties of biodegradable microspheres containing thioridazine hydrochloride.

Biodegradable microspheres of poly(DL-lactic-co-glycolic acid) (PLGA) containing thioridazine HCl were produced by four emulsion-solvent evaporation methods including an O/W emulsion method, an O/O emulsion method, a W/O/W multiple emulsion method, and a W/O/O/O multiple emulsion method. Gel permeation chromatography was used to determine the molecular weight of the polymer before and after processing. Resultant microspheres were either incubated in an oven at 40 degrees C, or stored in a desiccated chamber at 20 degrees C. Change in the molecular weight of the polymer was monitored as a function of time. Premature degradation of the polymer was evident in microspheres produced by the O/W conventional solvent evaporation method. Thioridazine HCl catalyzed hydrolysis of PLGA was evident in normalized molecular weight distribution plots of the O/W microspheres. The in vitro release of thioridazine HCl from multiphase microspheres produced by potentiometric dispersion was compared with the release of drug from conventional microspheres prepared from the same polymer. Release of thioridazine HCl from multiphase microspheres of the W/O/O/O type occurred by diffusion during initial stages of drug release.

Biocompatible Materials↗
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↗