Louis A. Luzzi

Preparation of controlled release anticancer agents I: 5-fluorouracil-ethyl cellulose microspheres

Microspheres of 5-fluorouracil have been prepared, using three grades of ethyl cellulose as wall forming materials, and utilizing a solvent evaporation technique under ambient conditions. An alcoholic solution of 5-fluorouracil and polymer was dispersed in liquid paraffin containing 33.3 per cent n-heptane. The effect of stirring rate, time of stirring, drug loading, and polymer grade on drug release in two different media were evaluated. The drug loaded particles were spherical in shape and had a diameter range of 25-200 mm and were suitable for incorporating into a gel base. Drug release studies in aqueous media, showed that acidic media provide a faster release rate than neutral media. The drug release study from an aqueous gel base preparation at pH 7.0 through a synthetic membrane was found to be promising for formulation of a gel-microsphere product for the treatment of skin lesions.

Coating charcoal with polyacrylate-polymethacrylate copolymer for haemoperfusion. I: Fabrication and evaluation

A potential haemoperfusion system has been developed using activated charcoal encapsulated with a polyacrylate-polymethacrylate copolymer. The film forms a coating of great mechanical strength around the charcoal particles, which is readily permeable to water and certain dissolved substances. The charcoal granules were coated with various membrane thicknesses consisting of a 2-10 per cent (by weight) film coat, using the modified method of non-solvent addition of Benita et al. (1985). The effect of various encapsulation variables such as stirring rate, rate of addition of non-solvent, percentage of coating polymer and concentration of a non-wall-forming polymer (PIB) in the non-solvent phase on adsorptivity, as well as the release of fine particles, were determined. The effect of coating thickness on the adsorption rate of the coated charcoal was investigated by constructing Higuchi diffusion model plots using methylene blue as a model adsorbate. It was found that the membrane permeability can be adjusted by changing experimental conditions to obtain high adsorption capacity along with a low level of released particles. Further, the effect of presoaking of the coated charcoal in purified water, normal saline, and 0.067 M phosphate buffer pH 7.4 (for 24 h at 37 degrees C) on the rate of adsorption of methylene blue was also evaluated.

Cosolvency of dimethyl isosorbide for steroid solubility

Dimethyl isosorbide (DMI), which is currently under investigation for its potential use as a pharmaceutical vehicle and drug permeation enhancer, is a water-miscible liquid with relatively low viscosity. The solubilization behavior of DMI as a cosolvent for nonpolar drugs was characterized via dielectric constant measurements of binary solvent systems containing DMI and either water, propylene glycol (PG), or polyethylene glycol (PEG). Evidence from the dielectric constant profiles and NMR studies suggest that DMI undergoes complexation with water and PG, but not with PEG, through hydrogen bonding interactions. The solvent complexation exhibited a major effect on the solubilities of prednisone, dexamethasone, and prednisolone in the mixed solvent systems. Maximum solubility of each drug was found to occur near a DMI/water or DMI/PG concentration ratio of 1:2. In the DMI–PEG mixed system, while there is no apparent interaction between DMI and PEG molecules, the solubility of prednisone was found to increase with decreasing dielectric constant.

A new approach to encapsulating nonsteroidal anti-inflammatory drugs. IV: Effect of cellulose derivatives with different functional groups on the bioavailability and gastric ulcerogenic activity of acidic as well as basic nonsteroidal anti-inflammatory drugs

The bioavailability and gastric ulcerogenic activity of oxyphenbutazone and glafenine (acidic and basic nonsteroidal anti-inflammatory drugs), coated with different cellulose derivatives were assessed in albino rats. The cellulose derivatives chosen have different functional groups, acidic (carboxymethyl cellulose), basic (chitosan) and neutral (hydroxypropylmethyl cellulose). The bioavailability was dependent on the drug and polymers. Generally, all the cellulose derivatives chosen decreased the gastric ulcerogenic activity of the drugs studied.

A new approach to encapsulating nonsteroidal anti-inflammatory drugs. I. Bioavailability and gastric ulcerogenic activity

Different classes of nonsteroidal anti-inflammatory drugs, NSAIDs, were separately coated with cationic (E) and anionic (L) Eudragit using the fluidized bed technique. The bioavailability and ulcerogenic activity of coated and uncoated drugs were assessed in rats. The cationic coat decreased the ulcerogenic activity in all classes of NSAIDs and increased the bioavailability only in acidic and enolic ones. The anionic coat, however, increased the bioavailability in basic NSAIDs.

A new approach to encapsulating nonsteroidal anti-inflammatory drugs. III. Coating acidic as well as basic nonsteroidal anti-inflammatory drugs with cellulose derivatives having different functional groups.

Acidic and basic nonsteroidal anti-inflammatory drugs were encapsulated with cellulose derivatives having different functional groups, acidic (carboxymethyl cellulose), basic (chitosan), and neutral (hydroxypropylmethyl cellulose). The properties of the microcapsules were studied and the interaction of the drugs with chitosan was assessed.

Coating charcoal with polyacrylate-polymethacrylate copolymer for haemoperfusion : the effect of the coat thickness on the adsorption capacity of the coated charcoal and its adsorptivity to small and middle size molecules

In this study, the effect of the coat thickness of polyacrylate-polymethacrylate copolymer on the adsorption capacity of activated charcoal to methylene blue as a model marker was investigated by constructing both Langmuir and Freundlich isotherms. It was found that the coat thickness significantly affected the adsorption coefficient of the coated charcoal to methylene blue as is reflected by the attractive forces between the adsorbent and the adsorbate. This effect is understandable as the membrane will act as a barrier between the adsorbent and the adsorbate. The coat thickness also had some effect on the adsorption capacity of activated charcoal but not as much as it affected the adsorption coefficient. The data followed the Freundlich isotherm more closely than the Langmuir equation. The effect of the coat thickness on the adsorption of selected drugs of different molecular size was also investigated using theophylline, paracetamol, sodium phenobarbital, creatinine and vitamin B12 as model drugs. The results showed that the adsorption patterns of theophylline, paracetamol and sodium phenobarbital were more or less similar. The apparent coating thickness did not affect the extent of adsorption of these model drugs and there was little effect on the adsorption rate especially during the first 15 min. The adsorption of vitamin B12 and creatinine showed completely different patterns which are discussed in detail.

A new approach to encapsulating nonsteroidal anti-inflammatory drugs. II. Physicochemical properties

Nonsteroidal anti-inflammatory drugs, NSAIDs, were encapsulated with cationic and anionic Eudragit polymers. The properties of the microcapsules were studied. The interactions, if any, between the polymers and NSAIDs were also investigated.

Design and evaluation of a rotating filter-magnetic basket apparatus: tablet and basket position

Abstract The authors have designed a dissolution device which combines the properties of a rotating filter device developed by Shah and a magnetic basket designed by Shepard et al. The effects of stirring, tablet and basket placement were investigated. Visualization of flow and dissolution patterns was possible by testing non-disintegrating salicylic acid tablets containing 3% phenolphthalein in 0.1 N sodium hydroxide solution. Dissolution experiments were conducted on non-disintegrating salicylic acid in pH 7.4 U.S.P. phosphate buffer at 37°C. For the tablet placement experiments one tablet face and the tablet land was coated so that only a single tablet face was available for dissolution. The data for the same size tablets placed at the side of the bottom and at the center of the bottom of the dissolution fluid container indicated the importance of exact placement of a tablet in a dissolution fluid container. The differences in face position of the tablet either with or without a magnetic basket present indicates the importance of face position which must be accounted for especially in the testing of double-layer sustained release products. Through the dissolution data and the visualization studies the authors have characterized the hydrodynamics of this device.

Coating charcoal with polyacrylate-polymethacrylate copolymer for haemoperfusion. II. Drug removal and polymer compatibility studies

The newly developed system of polyacrylate-polymethacrylate-coated charcoal, filled in a column has been tested for its efficiency in removing theophylline, as a model drug both from a buffer solution pH 7.4 and human plasma using a closed-circuit apparatus. Preliminary testing determined the capacity of the charcoal column and the effect of circulation rate of the buffer solution on the clearance of theophylline. It was found that the circulation rate does not significantly affect the clearance rate of theophylline, while the concentration of drug in the buffer solution has a considerable effect on the clearance of the drug, presumably due to the saturation of the column. The clearance of the drug from plasma in comparison to buffer solution was also investigated. It was found that more than 70 per cent of the drug was removed from the buffer solution within the first 15 min as compared with 65 per cent from plasma; with 95 per cent removed from buffer after 1 h in comparison to 93 per cent from plasma. The blood compatibility of the polymer was studied by incubating various concentrations (5-25 per cent w/v) of the polymer in blood for 30 min at 25 degrees C. A concentration of 5 per cent polymer was also incubated for a series of incubation times. The results indicated that with polymer concentrations up to 15 per cent there is no significant lysis of RBCs in comparison to a blank.(ABSTRACT TRUNCATED AT 250 WORDS)