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Biomedical subjects

A Gazzaniga

Publications and source records attributed to A Gazzaniga.

At least 37 records · Page 2Linked to original sources
PubMed1995

A physiochemical approach to the investigation of the stability of trimethoprim-sulfamethoxazole (co-trimoxazole) mixtures for injectables.

The stability of the trimethoprim/sulfamethoxazole (1:5, w/w) combination suitable for administration by injection was investigated to determine the nature of solid phases that can separate after dilution with infusion fluids. Phase-solubility analysis was performed on the binary system in water and in buffered aqueous media (pH 7 and 9), thus allowing a comprehensive picture of solid-solution compositions. Commercial samples of this combination were tested for solid phases separating after dilution with various infusion fluids. The interaction between trimethoprim and sulfamethoxazole, forming a 1:1 molecular compound with low solubility in water, is mainly responsible for the physicochemical properties of mixtures of these drugs in solution. Other solid phases (i.e., trimethoprim monohydrate and sulfamethoxazole emihydrate) can separate on long-term standing of solutions, depending on the value of the pH of the medium and the fluid used for dilution.

Calorimetry, Differential Scanning↗
PubMed1995

[Bioadhesives: rationale, state of the art and therapeutic potential].

Pharmaceutical research is going on the way to formulate drugs in dosage forms and delivery systems able to improve their biopharmaceutical properties. For some routes of administration, among them the transmucosal ones, such improvements may be reached by increasing the time and the nature of the contact between mucosal tissues and drug dosage forms via chemical or physical bioadhesive links. Biopharmaceutical AFI Study Group efforts were oriented in analyzing the actual state of the art in the field of bioadhesive drug delivery. Rationals of use of drug dosage forms with bioadhesive properties, analytical method of control of bioadhesion (both in vitro and in vivo) and therapeutical potentialities are the matter of this review.

Animals↗
PubMed1994

Epidermal growth factor in the topical treatment of herpetic corneal ulcers.

The tolerability and efficacy of epidermal growth factor (EGF) in the topical treatment of herpetic corneal ulcers in addition to topical acyclovir have been evaluated in a double-blind, placebo-controlled, randomized study in two groups of patients. The time required for complete reepithelialization of the cornea was recorded, and the data obtained were analyzed statistically. In the EGF group, the reepithelialization was significantly faster than in the control group. Tolerability of EGF was always excellent. These results indicate that EGF is safe and effective in reducing the healing time of herpetic corneal ulcers.

Acyclovir↗
PubMed1993

Ocular pharmacokinetics and pharmacodynamics in rabbits of ibopamine, a new mydriatic agent.

Ibopamine is an original dopamine analogue. The drug, instilled in the conjunctival sac, induces mydriasis and is well-tolerated. In the present study, we have investigated the pharmacokinetic and pharmacodynamic characteristics of ibopamine after ocular application. Ibopamine produces a dose-dependent mydriasis endowed with very interesting characteristics: rapid onset, marked pupil dilation and rapid return to normal pupillary diameter. Ibopamine is well absorbed through the cornea, it is rapidly hydrolysed by esterases to epinine and the mydriatic effect is correlated with the concentration of epinine in the aqueous humor. The results of the experiments with the alpha 1-antagonists bunazosin and thymoxamine, and with reserpine, suggest that the mydriatic effect of ibopamine is obtained by direct stimulation of the alpha 1-adrenergic receptors; pretreatment with bunazosin almost completely inhibits the mydriatic activity of ibopamine; the mydriasis is also antagonized by thymoxamine. Pretreatment with reserpine has no effect on the extent of the mydriasis induced by ibopamine.

Adrenergic alpha-Agonists↗
PubMed1993

Epidermal growth factor in the topical treatment of traumatic corneal ulcers.

The tolerability and efficacy of epidermal growth factor (EGF) in the topical treatment of traumatic corneal ulcers have been evaluated in a double-blind, placebo-controlled, randomized study in two groups of patients. The time required for complete reepithelialization of the cornea was recorded, and the data obtained were analyzed statistically. In the EGF group the reepithelialization was significantly faster than in the control group. Tolerability of EGF was always excellent. These results indicate that EGF is safe and effective in reducing the healing time in the management of superficial corneal lesions.

Administration, Topical↗
PubMed1992

Lecithin organogel as matrix for transdermal transport of drugs.

Organogels obtained by adding small amounts of water to a solution of lecithin in organic solvents were studied as matrices for the transdermal transport of drugs. Gels obtained from isopropyl palmitate and cyclooctane were used (molar ratios of water to lecithin of 3 and 12, respectively). Preliminarily histological studies showed that the gels have no harmful effect when applied to the skin for prolonged periods. Data relative to the stability of the organogels with time are also presented. Scopolamine and broxaterol were used as model drugs, and the transdermal experiments were done with a Franz diffusion cell and human skin obtained from plastic surgery. The transport rate of scopolamine obtained with the lecithin gels was about one order of magnitude higher than that obtained with an aqueous solution of the drug at the same concentration. In contrast, the transport rates of scopolamine obtained with the microemulsion solution prior to gelation (molar ratio of water to lecithin, 0) were not different from those obtained with the gel. The same variations in transport rates were observed for broxaterol, in which case the flux through the skin was directly proportional to the concentration of drug in the gel. At a concentration of broxaterol of 75 mg/mL in the donor gel, the flux was 47 micrograms.h-1.cm-2. Because preliminary results showed that transdermal transport is successful with amino acids and peptides also, it is concluded that lecithin gels may be efficient vehicles for the transdermal transport of various drugs.

Adult↗
PubMed1992

Dopamine, dopaminergic drugs and ocular hypertension.

The study refers to the clinical experiences performed with several D1 and D2 dopaminergic receptors agonists in 20 patients with high tension open angle glaucoma. The substances were administered topically as eye drops as well as an ocular eye bath. The parameter examined was intraocular pressure (IOP). The substances taken in consideration were: Dopamine, Ibopamine (dopamine analog), Fenoldopam and 3B90 (D1-receptor agonists) and Bromocriptine (dopaminergic agonist with higher affinity for D2 than for D1-receptors). It has been shown that all selective D1-receptors agonists induce a significant increase in IOP only in eyes with hydrodynamic disorders (p < 0.001). Such hypertensive effects could not be antagonized either by topically administered dopaminergic antagonists (Sulpiride, D2-receptors antagonist, and Haloperidol, non-selective dopaminergic antagonist) or by the pretreatment with the commonly used topical antiglaucomatous drugs. The only substance which proved able to inhibit the IOP increase induced by the D1-receptors agonists was the D1-selective antagonist SCH-23390, suggesting that IOP increase may be a result of a stimulation of the D1-receptors. The authors hypothesize that dopaminergic system may play a role in the regulation of aqueous humor hydrodynamics.

Adult↗
PubMed1992

Ocular pharmacokinetics of thiamphenicol in rabbits.

The ocular pharmacokinetics of thiamphenicol (TAP, CAS 15318-45-3) was studied in rabbits by means of the assessment of its ocular and systemic absorption, and urinary excretion after instillation of 0.5% TAP eye drops. TAP concentrations in aqueous humor, plasma and urine were evaluated by a coupled LC/GC method (detection limit = 0.1 ng/ml), because the necessity to have a technique much more sensitive than the traditional chromatographic ones available in order to quantify the very low drug concentrations in biological fluids produced by the ocular treatment, and generally by a topical administration. The intravenous route was chosen as reference and allowed the absolute bioavailability to be estimated. TAP proved to be well absorbed through the cornea with the peak aqueous humor concentration of 110 ng/ml at 45 min following the instillation. The good ocular absorption of TAP was confirmed by the plasma concentrations observed after instillation of 0.5% eye drops. In any case, these concentrations were more than 1000 times lower than those observed after the intravenous treatment at the dose normally used for infectious diseases, allowing to exclude any systemic toxicity of TAP eye drops. The absolute ocular bioavailability was 16.2% when estimated from the AUC values and 34.0% from the cumulative urinary excretion values.

Administration, Topical↗
PubMed1992

Activity and pharmacokinetics of a new oral dosage form of soluble ibuprofen.

The pharmacokinetics and the relative bioavailability of a soluble granular form (sachets) of a pharmaceutical formulation containing ibuprofen (CAS 15687-27-1) and 1-arginine were investigated in healthy volunteers. Two granular dosage forms were evaluated, 200 and 400 mg, in comparison with the commercial equivalents (tablets). After the oral administration of both granular dosage forms, a quicker absorption and a significantly higher plasma bioavailability of ibuprofen in the first hour following the treatment than after tablets administration were observed. The mean values of peak plasma concentration (microgram/ml) were 26.1 and 56.4 after treatment with 200 and 400 mg sachets respectively vs. 16.3 and 43.0 after treatment with 200 and 400 mg tablets. The mean values of peak time were 16.9 and 24.4 min after treatment with 200 and 400 mg sachets respectively vs. 90.0 and 63.7 min after treatment with 200 and 400 mg tablets. The shortening in the absorption time and the increase in the plasma concentrations did not involve a quicker drug elimination nor cause any changes in the bioavailability (mean values of the relative bioavailability indexes of 0.98 for 200 mg dosage form and 1.02 for the 400 mg one). The analgesic activity of soluble ibuprofen 400 mg was compared with that of ibuprofen 400 mg tablets in patients with osteo-articular pain, according to a single dose, double-blind cross-over balanced design. The results showed that the soluble granular form is able to determine an analgesic effect significantly quicker and higher than that of tablets.

Adult↗
PubMed1989

Determination by coupled high-performance liquid chromatography-gas chromatography of the beta-blocker levomoprolol in plasma following ophthalmic administration.

Levomoprolol is a beta-blocking agent used in the topical treatment of glaucoma. The necessity for comparing the plasma levels of a drug administered by the ophthalmic route with those obtained following systemic treatment requires increasingly sensitive methods in order to determine the low plasma concentrations produced by the administration of eye drops. On-line high-performance liquid chromatography-gas chromatography and concurrent solvent evaporation proved to be advantageous in the determination of levomoprolol in human plasma. Levomoprolol was determined by capillary gas chromatography (GC) with electron-capture detection (ECD) after solid-phase extraction from plasma and derivatization. Quantitation was based on the internal standard method. The detection limit of 0.2 ng/ml is 50 times lower than that obtained with previous GC methods involving on-column injection and ECD.

Adrenergic beta-Antagonists↗
PubMed1989

Swelling-restricted minimatrices for controlled release of drugs. Preliminary in-vivo studies.

A preliminary in-vivo study was performed on a new modified release system which contained diltiazem hydrochloride. The system consisted of swellable minimatrices that were coated with an acrylic polymeric film. The film thickness, because of its pH-dependent solubility, might represent a critical variable with regard to in-vivo release. In order to evaluate the influence of such a variable on in-vivo behaviour, two minimatrices formulations with differing film thickness were tested versus a commercial tablet. The in-vivo study, which was based on a balanced incomplete block design, involved six volunteers in two sequences. The drug was quantified in plasma by an HPLC method. Computation and statistical analysis of pharmacokinetic parameters were performed by means of SIPHARR package (Simed, F). The results show that the approach of film coating, in order to modify the release rate from minimatrices, is feasible, but it must be improved; in particular the results point to the necessity of reducing the film susceptibility to pH changes.

Adult↗
PubMed1988

Multicenter open trial of cefotetan and cefoxitin in elective biliary surgery.

The present study was performed in two phases. In phase I, 112 patients were randomized to either 2 g cefotetan as a single prophylactic dose or 2 g cefoxitin every 6 hours for a maximum of 4 doses; phase II included 148 patients who were randomized to either 1 g cefotetan as a single dose or cefoxitin dosed as in phase I. The randomization was 2:1 cefotetan to cefoxitin in both phases. Nonevaluability rates were 10 percent for the cefotetan patients and 22 percent for the cefoxitin patients, the majority being due to dosing errors. Demographic characteristics demonstrated 88 percent to be female, 81 percent to be less than 65 years of age, and the average weight to be 165 lb. There were no differences in these characteristics among the groups. Common duct exploration was performed in 6 percent of the 2 g cefotetan patients, 9 percent in the 1 g cefotetan patients, and 13 percent in the 2 g cefoxitin patients. There were five clinical failures of prophylaxis: one wound infection in the 2 g cefotetan patients, one wound infection and one drain tract infection in the 1 g cefotetan patients, and one wound infection and one case of cholangitis in the 2 g cefoxitin patients. The clinical success rates were 98 percent in the 2 g cefotetan patients, 98 percent in the 1 g cefotetan patients, and 97 percent in the 2 g cefoxitin patients.

Aged↗
PubMed1988

Swelling-activated drug delivery systems.

A previous paper dealt with the preparation of an in vitro programmable zero-order drug delivery system in which the area of the surface exposed to the dissolution medium and the macromolecular relaxation of polymer controlled the release of the drug. In the present study, the preparation of similar delivery systems is described, in which differing drugs and polymers were used to ascertain the mechanism governing the drug-release kinetics. The movement of the interfaces between solvent and system was measured during drug release in systems with varying composition. The results indicate that the synchronization of the movement of swelling and eroding fronts at the solvent-system interface determines the achievement of the linear-release kinetics of such swelling activated systems and that the swelling and dissolution characteristics of the polymer employed for core preparation govern front movement.

Chemical Phenomena↗
PubMed1988

Drug/polymer matrix swelling and dissolution.

The swelling and dissolution behavior of pharmaceutical systems containing a drug and a polymer can be analyzed by a mathematical model which predicts the drug released and the gel layer thickness as a function of time. It is possible to approximate the values of several of the physicochemical parameters of this model in order to obtain an order-of-magnitude analysis of the tablet dissolution process. Selected experimental results of tablet dissolution and drug release are analyzed and conclusions are made about the importance of the drug and polymer content and solubility in the release behavior.

Chemical Phenomena↗
PubMed1985

A route to the total synthesis of iso-LTB4 system.

The convergent synthesis of the iso-Leukotriene B4 (XVI) (as diastereoisomeric mixture with the desired geometry), by Wittig's condensation of the two precursor synthons at 6 (VI) and 14 C (XIV), starting from the common cyclic acrylaldehyde dimer (I), is reported.

Chemical Phenomena↗