Ultrasonic degradation of aspirin in mixed solvent systems.
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Aspirin↗
Biomedical subjects
T E Needham
Publications and source records attributed to T E Needham.
Blood levels following multiple oral dosing of chlorpheniramine conventional and controlled release preparations.
An examination of steady-state performance of chlorpheniramine conventional versus controlled release products was conducted using 15 male subjects in a 3-way crossover study with a 2-week washout period between studies. The study was designed to determine if chlorpheniramine formulations provide consistent pharmacokinetic performance between individual units upon going from single dose to multiple dose therapy. In addition, the validity of predicting steady-state levels for these kinds of products using only single oral dose data was examined. The dosage forms evaluated were a conventional 4 mg tablet, and 8 mg barrier coated-bead capsule, and an 8 mg repeat action tablet. Multiple doses of each product were orally administered to each subject for 6 days prior to the study day to achieve steady-state levels and on the actual study day. Serum samples were collected at specific time intervals on the study day, and chlorpheniramine levels assayed by HPLC. Pharmacokinetic analysis was based on a two-compartment open model. The mean plasma elimination half-lives of the various dosage forms were in the range 24.5-25.4 h. There was no rapid release of drug from the controlled release products nor did they have drug release problems during the dosing interval. Good agreement was obtained between predicted average drug concentration at steady-state and drug concentration actually present for all the formulations studied. Based upon comparative examination of AUC, Cmax, and fraction of dose absorbed data, the controlled release products administered every 12 h were comparable in performance to a conventional release tablet administered every 6 h. Since the half-life of chlorpheniramine is approximately 1 day, therapeutic management may possibly be gained with dosing the patient once daily with a controlled release product or twice daily with a conventional tablet.
Adolescent↗
Development and evaluation of nasal formulations of ketorolac.
Ketorolac tromethamine is a potent non-narcotic analgesic with moderate anti-inflammatory activity. Clinical studies indicate that ketorolac has a single dose efficacy greater than morphine for postoperative pain and has excellent applicability in the emergency treatment of pain. Due to incomplete oral absorption of ketorolac, several approaches have been tried to develop a nonoral formulation in addition to injections, especially for the treatment of migraine headache. The aim of our study was to develop a nasal formulation of ketorolac with a dose equivalent to the oral formulation. A series of spray and lyophilized powder formulations of ketorolac were administered into the nasal cavity of rabbits, and their pharmacokinetics profiles were assessed. The spray and powder formulations were compared through their pharmacokinetics parameters and absolute bioavailability. Drug plasma concentration was determined using solid phase extraction, followed by an HPLC analysis. Nasal spray formulations were significantly better absorbed than powder formulations. A nasal spray formulation of ketorolac tromethamine showed the highest absorption with an absolute bioavailability of 91%. Within 30 min of administration, the plasma concentration was comparable to that resulting from an intravenous injection. The absolute bioavailability of a solution of ketorolac acid was 70%. Apparently, the dissolution of ketorolac acid into the mucous layer limits its absorption. There were no significant differences in absorption between different powder formulations. Even the reduction of particle size from 123 microm to 63 microm did not indicate better absorption of ketorolac tromethamine from powder formulations. Interestingly, the absolute bioavailability of ketorolac tromethamine from a powder formulation is only 38%, indicating that the drug may not be totally released from the polymer matrix before it is removed from nasal epithelium by mucociliary clearance.
Administration, Intranasal↗
Biopharmaceutical evaluation of a tablet dosage form made from ethyl cellulose encapsulated aspirin particles.
Ethyl cellulose encapsulated aspirin particles, suitable for preparation of direct compression tablets were prepared by the solvent evaporation method. Ethyl acetate was used as a solvent for the polymer in combination with a saturated solution of aspirin as the dispersing medium to prevent partitioning and drug loss. This resulted in a high yield of free-flowing, non-aggregated particles. In vitro-in vivo evaluations of the experimental aspirin tablets (made by direct compression of ethyl cellulose encapsulated particles) and three different commercial aspirin products (a conventional tablet, a timed-release tablet, and a timed-release caplet) were undertaken. Comparison of the dissolution in acidic media at pH 1.2 showed different release profiles for these products. While the conventional tablet and the timed-release caplet showed the highest and the lowest rate of release, respectively; the timed-release tablet and the experimentally made tablet revealed an intermediate rate and very similar release profiles. The cumulative urinary excretion data collected in a complete crossover study, using five healthy subjects further indicated that the experimental tablet has an in vivo availability identical to that of the timed-release tablet.
Adult↗
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.
Acrylic Resins↗
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)
Acrylic Resins↗
Coating charcoal with polyacrylate-polymethacrylate copolymer for haemoperfusion. III: The effect of the coat thickness on the adsorptioncapacity 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.
Acrylic Resins↗
Effect of cyclosporine A formulations on bovine corneal absorption: ex-vivo study.
The purpose of this study was to evaluate, in an ex-vivo study, the absorption of cyclosporine A on bovine cornea after 24 h contact with various drug delivery systems containing 1% cyclosporine A and in comparison with an olive oil formulation as the reference vehicle for cyclosporine A. The different formulations studied were poly(acrylic acid) polymeric gels in aqueous/non-aqueous solvents, polyisobutylcyanoacrylate nanocapsules, and a combination of both formulations. The histological effects of these formulation on corneal cells after 24 h of contact were also studied. The lowest absorption rate of cyclosporine A was found using olive oil with a percent absorption of 2.52 +/- 1.52% (259 +/- 171 micrograms/g cornea). The three formulations developed for this study, nanocapsules, poly(acrylic acid) polymeric gel and nanocapsules gel showed significantly better absorption of CsA than olive oil, with a mean percent absorption of 5.81 +/- 2.04% (621 +/- 218 micrograms/g cornea), 6.09 +/- 2.93% (651 +/- 313 micrograms cornea) and 7.92 +/- 2.55% (847 +/- 273 micrograms/g cornea) respectively. As we studied the penetration of cyclosporine A into the different layers of the cornea, we observed that for all formulations, CsA remained at the corneal surface and did not penetrate the whole cornea. The histological study showed that olive oil, nanocapsules and poly(acrylic acid) gel in aqueous/non-aqueous solvents show some modifications on the cornea, contrary to the nonocapsules gel which did not indicate any toxic effect. The nanocapsule gel, with the highest percent absorption along with its margin of safety on the cornea, seems to present a new promising drug delivery system for ocular administration.
Acrylic Resins↗
Emulsion formulations of testosterone for nasal administration.
The nasal route has received a great deal of attention due to the many advantages of nasal delivery over parenteral administration. The male sex hormone testosterone is ineffective when administered orally due to its gut wall and first-pass metabolism. Therefore, an alternative method for delivery would be the intranasal route, if the lack of aqueous solubility can be overcome. In this study a new approach to emulsion formulations of the drug has been proposed based on the hypothesis that increased absorption is possible upon solubilization of the drug and/or prolongation of the formulation residence time in the nose. Three differently charged testosterone submicron size emulsion formulations with various zeta potentials (+24.8, -23.0 and 0.06 mV) were prepared as nasal spray formulations. A dose of approximately 3.8 mg testosterone per rabbit was administered to four rabbits and the bioavailability of the emulsion formulations was assessed and compared with an i.v. formulation via solid-phase extraction, followed by an HPLC analysis method. Statistical analysis of the normalized data indicated a bioavailability of 55, 51 and 37% for positively, negatively and neutrally charged emulsions respectively. The results of this study strongly suggest that emulsion formulations have some potential to be considered for nasal delivery. Further, both the positively and negatively charged emulsion formulations provided a better bioavailability than the neutral charged emulsion, probably indicating that the charged particle interactions between emulsion globules and the mucus layer prolong the contact of drug with nasal membrane thus enhancing drug absorption.
Absorption↗