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Biomedical subjects

G E Peck

Publications and source records attributed to G E Peck.

At least 19 recordsLinked to original sources

Drug physical state and drug-polymer interaction on drug release from chitosan matrix films.

Four different grades of chitosan varying in molecular weight and degree of deacetylation were used to prepare chitosan films. Salicylic acid and theophylline were incorporated into cast chitosan films as model acidic and basic drugs, respectively. Crystalline characteristics, thermal behavior, drug-polymer interaction and drug release behaviors of the films were studied. The results of Fourier transform infrared and solid-state 13C NMR spectroscopy demonstrated the drug-polymer interaction between salicylic acid and chitosan, resulting in salicylate formation, whereas no drug-polymer interaction was observed in theophylline-loaded chitosan films. Most chitosan films loaded with either salicylic acid or theophylline exhibited a fast release pattern, whereas the high viscosity chitosan films incorporated with salicylic acid showed sustained release patterns in distilled water. The sustained release action of salicylic acid from the high viscosity chitosan films was due to the drug-polymer interaction. The mechanism of release was Fickian diffusion control with subsequent zero order release. It was suggested that the swelling property, dissolution characteristics of the polymer films, pK(a) of drugs and especially drug-polymer interaction were important factors governing drug release patterns from chitosan films.

Calorimetry, Differential Scanning↗

Physical properties and molecular behavior of chitosan films.

Chitosan films, varying in molecular weight and degree of deacetylation, were prepared by a casting technique using acetic acid as a dissolving vehicle. The physicochemical properties of the films were characterized. Both molecular weight and degree of deaceylation affected the film properties. Powder X-ray diffraction patterns and differential scanning calorimetry thermograms of all chitosan films indicated their amorphous state to partially crystalline state with thermal degradation temperature lower than 280-300 degrees C. The increase in molecular weight of chitosan would increase the tensile strength and elongation as well as moisture absorption of the films, whereas the increase in degree of deacetylation of chitosan would either increase or decrease the tensile strength of the films depending on its molecular weight. Moreover, the higher the degree of deacetylation of chitosan the more brittle and the less moisture absorption the films became. All chitosan films were soluble in HCl-KCl buffer (pH 1.2), normal saline, and distilled water. They swelled in phosphate buffer (pH 7.4), and cross-linking between chitosan and phosphate anions might occur Finally, transmission infrared and 13C-NMR spectra supported that chitosan films prepared by using acetic acid as a dissolving were chitosonium acetate films.

Administration, Cutaneous↗

Accelerated fluid bed drying using NIR monitoring and phenomenological modeling.

A "fast-drying" method to accelerate the fluid bed drying process is presented. It relies on concepts of heat and mass transfer with real-time near-infrared (NIR) monitoring of moisture. Triplicate trials show that fast drying can reduce granulation drying time by half over single-temperature cycles. The product is equivalent in every way tested to material made using a conventional cycle even though the inlet temperature throughout the constant-rate stage was higher than the melting point of the compound. Tablets made from the fast-dried granulation exhibit equivalent physical characteristics to tablets made from granulations dried at a single, lower temperature.

Anti-Inflammatory Agents, Non-Steroidal↗

The effect of formulation on radioiodide thyroid uptake in the hyperthyroid cat.

This investigation was designed to compare in vitro dissolution profiles from sodium iodide capsules with radioiodide thyroid uptake in hyperthyroid cats using sodium iodide capsules prepared with a formulation exhibiting a complete release of radioiodide (I-123) in vitro and a formulation with an incomplete release of radioiodide. In vitro dissolution profiles for I-123 sodium iodide capsules with two different formulations were determined using the USP XXIII dissolution test. The two formulations studied in vitro were sodium phosphate dibasic powder with 1% magnesium stearate and calcium phosphate dibasic powder with 3% magnesium stearate. By 20 min after initiation of the dissolution test, over 95% of the I-123 was released from capsules of sodium phosphate dibasic powder. The capsules of calcium phosphate dibasic powder reached 75% at 65 min, with no further release occurring thereafter. There was a statistically significant difference in the dissolution profiles of the two formulations. The thyroid uptake of I-123 from capsules exhibiting complete release and incomplete release of radioiodide was determined in hyperthyroid cats. At 4 hr, the mean percentage thyroid uptake value for sodium phosphate dibasic powder with 1% magnesium stearate (complete release formulation) was 12.0% compared to 9.4% for calcium phosphate dibasic powder with 3% magnesium stearate (incomplete release formulation); at 24 hr, the values were 34.4% compared to 23.7%. The data suggest that the incomplete dissolution profile observed in vitro may correlate with a reduction in the bioavailability of the radioiodide in vivo. However, using the Wilcoxon signed rank test, statistically significant differences did not occur between the complete release formulation and incomplete release formulation at either 4 hr or 24 hr (p > .05). The results of the in vivo study with five hyperthyroid cats were not conclusive due to the variability in response between individual cats.

Abdomen↗

Pharmaceutical granulation and tablet formulation using neural networks.

Current-day pharmaceutical formulation may be trial and error in nature due to the absence of a clear relationship between the formulation characteristics (output variables) and the material and process variables (input variables). Neural networks are networks of adaptable nodes, which through a process of learning from task examples, store experiential knowledge and make it available for prediction. Prediction of a model granulation and tablet system characteristics from the knowledge of material and process variables utilizing neural networks is the basis of this presentation. The formulation design contained the following variables: granulation equipment, diluent, method of binder addition, and the binder concentration. The material, process, granulation evaluation, and tablet evaluation data of the formulations were used as the data set for training and testing of the neural network models. A comparison of the neural network prediction performance with that of regression models was also done. Both the granulation model and the tablet model converged fairly rapidly in the training step. In the testing step, the predictions for all granulation model variables (geometric mean particle size, flow value, bulk density, and tap density) were satisfactory. In the tablet model, the predictions for disintegration and thickness were also satisfactory. The predictions for hardness and friability were less than satisfactory. Two situations where the neural network may not perform adequately are discussed. The neural network prediction is better or comparable for all the predicted variables in this study compared to regression methods. The results clearly show the applicability of neural networks to formulation modeling.

Caffeine↗

Solid-state nuclear magnetic resonance (NMR) spectra of pharmaceutical dosage forms.

Solid-state 13C NMR spectra of tablets or capsules of prednisolone, enalapril maleate, lovastatin, simvastatin, ibuprofen, flurbiprofen, mefenamic acid, indomethacin, diflunisal, sulindac, and piroxicam were obtained in the CP/MAS mode at 50 MHz. These studies show that (1) solid-state NMR spectroscopy can detect the active ingredients in low-dose tablets and capsules; (2) the use of interrupted decoupling often results in suppression of resonances due to excipients, thereby allowing better detection of resonances from the drug; and (3) the technique permits discrimination between two prednisolone polymorphs present in tablets obtained from various manufacturers even though the tablets contain only approximately 5% (w/w) of the drug.

Anti-Inflammatory Agents, Non-Steroidal↗

Evaluation of moisture sorption by tablet cores containing superdisintegrants during the aqueous film coating process.

A physical-chemical analysis of the extent of sorption of water by tablets containing superdisintegrants was carried out following the aqueous film coating of formulated tablets. Characterization of the uncoated and coated tablet properties was conducted using thermogravimetric analysis, differential scanning calorimetry, mercury intrusion porosimetry, and measurement of the tablet tensile strength. Tablet residual moisture content, pore system characteristics, tensile strength, and glass transition temperature of the amorphous polymer components of the tablet matrix were significantly affected after the coating operation. These findings were attributed to the penetration of water from the aqueous film coating solution into the tablet matrix.

Absorption↗

The effect of swelling characteristics of superdisintegrants on the aqueous coating solution penetration into the tablet matrix during the film coating process.

The mechanism and the extent of sorption of water molecules by tablets containing superdisintegrants and microcrystalline cellulose, following the aqueous film coating of formulated tablets, were investigated. The penetration of water from the coating solution into the tablet matrix resulted in significant changes in physical properties of the coated tablet cores, such as residual moisture content, tensile strength, and pore-size distribution. The swelling and the morphological characteristics of each individual disintegrant compound and microcrystalline cellulose were found to have important implications on the extent of penetration of water from the aqueous film coating solution. A hypothesis concerning the interaction between microcrystalline cellulose and the superdisintegrant particles present in the tablet matrix is proposed.

Cellulose↗

The effect of aluminum hydroxide dissolution on the bleeding of aluminum lake dyes.

The effect of pH on the bleeding of FD&C yellow No. 5 aluminum lake and FD&C red No. 40 aluminum lake was investigated. The pH-bleeding profiles corresponded to the pH-solubility profile of aluminum hydroxide. The similarity of the bleeding profiles of both lake dyes and the pH-solubility profile of aluminum hydroxide indicates that pH related bleeding, other than that occurring by competition with anions, is a result of dissolution of the aluminum hydroxide substrate. This dissolution is related to the properties of the substrate rather than to the structure of adsorbed dye.

Aluminum Hydroxide↗

A statistical approach for the development of an oral controlled-release matrix tablet.

Tablet matrix compositions for optimized prolonged release were selected by surface response methodology. The extreme vertices experimental design was used to develop a surface response model which mathematically defined the release of active component from the tablet matrix as controlled by the percentage of the excipient components. The model, a statistical quadratic equation with a standard error of 3.3, was validated for accurate prediction of drug release profiles and used to identify optimum formulations. This study demonstrated a new application of the extreme vertices experimental design, an efficient method for evaluating a complex mixture system for controlled release, where specific constraints are placed on one or more of the components.

Administration, Oral↗

The effect of moisture content on the compression properties of maltodextrins.

The effect of moisture content on the compression properties of maltodextrin powders obtained by different degrees of hydrolysis (depolymerization) of corn starch has been studied using the yield pressure determined from the Heckel plot and the compact tensile strength measured by the diametrical compression method. An increase in the moisture content of the powder reduced the yield pressure and improved the densification for all five maltodextrins evaluated. At the same moisture level, the extent of densification which occurred during compaction was greater for maltodextrins with a lower degree of polymerization. Compacts produced by maltodextrins with a lower degree of polymerization also exhibited a greater tensile strength for a given pressure at a moisture content below 8.0%. However, further increase in moisture content resulted in a decrease in compact tensile strength for maltodextrins having a lower degree of polymerization. Despite the significant difference in compression behaviour, the five maltodextrins did not show noticeable differences in crystallinity as revealed by their x-ray powder diffraction pattern.

Crystallization↗

Evaluation of the sorbent suspension reciprocating dialyser in the treatment of overdose of paracetamol and phenobarbitone.

Poisoning with paracetamol (acetaminophen) and phenobarbitone is a common occurrence in the United States and Europe. The removal efficiency of these drugs by a sorbent suspension reciprocating dialyser (SSRD) has been investigated. The SSRD is a parallel plate dialyser with a reciprocating blood flow and free mobile sorbent suspension composed of charcoal and zeolites. This arrangement provided a system with minimal sorbent saturation. High performance liquid chromatography was used for the quantification of the drugs in aqueous and serum fluids. The in-vitro removal efficiency of the dialyser was studied by dialysing a large volume of the drug in solution for 12 to 16 h. The removal efficiency remained relatively constant up to 10 h of dialysis. The in-vivo dialysis studies were performed using normal dogs. Large doses of the drugs were administered orally or intravenously to achieve high blood levels. The clearance values obtained from these studies were comparable with, or in excess of, the values reported in the literature for conventional dialysers. The major advantage of the SSRD is the ability of the unit to be used for prolonged dialysis and to provide a system with minimal sorbent saturation due to mixing and interchange of sorbent granules next to the membrane surface.

Acetaminophen↗

Effect of shear on the apparent viscosity of amorphous carbonate ion containing aluminum hydroxide suspensions.

The application of shear to carbonate ion containing aluminum hydroxide suspensions caused a change in the apparent viscosity by two possible mechanisms: change in the surface charge because of desorption of specifically adsorbed carbonate ion, and aggregate dispersal and formation of more extensive particle networks. The desorption of specifically adsorbed carbonate ion is related to the expansion of the air-liquid interface during shear. Shear-inducing processing equipment which generates a minimal amount of new air-liquid interface was found to produce the least change in pH and, consequently, in surface charge. However, viscosity increases caused by aggregate dispersal and formation of more extensive particle networks may occur without a shear-induced change in surface charge.

Aluminum Hydroxide↗

Role of water in the aging of aluminum hydroxide suspensions.

The rate of acid neutralization of anhydrous suspensions of amorphous aluminum hydroxide in methanol did not change during aging. At low water content, when all of the water was adsorbed, an initial decrease in the rate of acid neutralization was observed but no further change occurred during aging. When enough water was present to exceed the adsorptive capacity and produce water in the bulk methanol, the initial rate of acid neutralization decreased and a decrease in the rate of acid neutralization also occurred during aging. The decrease in rate of acid neutralization during aging is believed to be due to polymorphic transformation of the amorphous aluminum hydroxide and aggregation. The change caused by aggregation could be reversed by dehydration or sonication, but the change due to polymorphic transformation could not be reversed.

Aluminum Hydroxide↗

Mechanism of freeze-thaw instability of aluminum hydroxycarbonate and magnesium hydroxide gels.

The effect of freeze-thaw cycles on the physical stability of aluminum hydroxycarbonate and magnesium hydroxide gels was studied. Coagulation following a freeze-thaw cycle, leading to the formation of visible aggregates, affected the content uniformity of both gels. The freeze-thaw cycles did not affect the crystal form or surface characteristics of the gels as determined by X-ray powder diffraction and point of zero charge, but caused a slight reduction in the rate of acid neutralization and a large increase in the rate of sedimentation. The greatest effect was observed after the first freeze-thaw cycle. While the duration of freezing was not a factor, the rate of freezing was important and was inversely related to the aggregate size. The aggregates which formed following a freeze-thaw cycle were not redispersed by shaking, but were reversed by ultrasonic treatment or homogenization. The adsorption of polymers or surface-active agents prior to freezing reduced and, in some cases, prevented the formation of aggregates. The physical instability produced by a freeze-thaw cycle was explained by the modified DLVO theory. The force exerted on the particles by the growing ice crystals forced the particles into the primary minimum, producing strong interparticle attraction. On thawing, simple agitation did not provide enough force to overcome the attractive force of the primary minimum. Adsorption of polymers or surface-active agents increased the steric repulsive force and prevented the particles from reaching the primary minimum.

Aluminum Hydroxide↗

Quantitative evaluation of pharmaceutical effervescent systems I: Design of testing apparatus.

Two new devices were developed to monitor the reactivity of pharmaceutical effervescent systems. The first method monitored carbon dioxide pressure generation during the effervescent reaction in a plastic pressure vessel fitted with a pressure gauge. The second method monitored weight loss, attributed to carbon dioxide loss to the atmosphere, by means of a double cantilever beam and an electromagnetic proximity transducer. In the pressure device, the quantification of an effervescent reaction was accomplished by measuring the dissolution time of the effervescent system and the pressure generated. Quantification of an effervescent reaction using the beam device utilized the total carbon dioxide weight loss, the rate of weight loss, and the effervescent reaction lag time.

Bicarbonates↗