0000000000077781
AUTHOR
T.m. Garrigues
Stability of a Parenteral Formulation of Betamethasone and Levobupivacaine
Background: The therapeutic management of syndromes presenting simultaneously pain and inflammation often requires the administration of anesthetic and corticosteroid drugs by epidural administration. In this article, we studied a mixture that combines betamethasone and levobupivacaine, which demonstrates prolonged analgesic effects. To our knowledge, the stability of such a mixture in epidural solution has not been examined. Objective: To evaluate the chemical, physical, and microbiological stability of an extemporaneously prepared mixture. Methods: A solution of betamethasone acetate 1 mg/mL, betamethasone phosphate 1 mg/mL, and levobupivacaine hydrochloride 0.83 mg/mL was prepared in sa…
Biophysical Models as an Approach To Study Passive Absorption in Drug Development: 6-Fluoroquinolones
A preliminary study attempting to assess and explain the intestinal absorption of a series of antibacterial 7-piperazinyl-6-fluoroquinolones is presented. The synthesis, n-octanol partition coefficients, intrinsic rat gut in situ absorption rate constants, and in vitro antibacterial activity data found for these homologous compounds are described. A fluorimetric, reverse-phase HPLC method was performed for the quantification of the quinolones in absorption and partition samples. Equations based on two classic biophysical absorption models are given for predicting the intrinsic absorption features of the series according to the partition data or merely single structural parameters. In situ a…
Nortriptyline hydrochloride skin absorption: development of a transdermal patch.
The influence of propylen glycol (PG), ethanol, and oleic acid (OA) on nortriptyline hydrochloride (NTH) penetration through human epidermis was studied in vitro at two different pH values (5.5 and 7.4). The influence of lactic acid and polysorbate 80 was studied for a pH of 5.5. Permeation studies through Heat Separated Epidermis, as well as the enhancing effect of the different vehicles, showed a pH dependency. A pH value of 5.5 in the donor solution decreases significantly the permeability coefficient (Kp) with respect to a pH value of 7.4 (0.011+/-0.004 x 10(-6) versus 0.36+/-0.04 x 10(-6)cm/s). The vehicles showed an increasing enhancement effect in the order: polysorbate 80>ethanol/PG…
In Vitro Percutaneous Penetration of Acyclovir from Solvent Systems and Carbopol 971-P Hydrogels: Influence of Propylene Glycol
The mechanism underlying propylene glycol (PG) effects on acyclovir (ACV) penetration through human epidermis were studied. Solvent systems and Carbopol gels containing increasing percentage of PG (from 0% to 70%, w/w) were used. Viscosity studies of both vehicles were carried out to characterise the influence of rheological behaviour. In solvent systems skin permeation values of ACV increase as the concentration of PG increase yielding a maximum enhancement ratio (ER = 10) for 70% PG. The release rate of ACV from gels was determined. Higuchi's model was used to estimate the apparent diffusion coefficient of the drug. These values show a decrease as the content of PG in the vehicle increase…
Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects.
The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair…
Nortriptyline for smoking cessation: Release and human skin diffusion from patches
Abstract The objective of this work was to develop a simple and inexpensive transdermal formulation containing Nortriptyline Hydrochloride (NTH) for smoking cessation support therapy. Hydroxypropyl-methyl-cellulose was chosen as polymer and a mixture of transdermal enhancers (selected from previous research) was incorporated. The formulations were characterised in terms of appearance, thickness, uniformity of NTH content, release and skin permeation. Release studies demonstrated controlled release for four formulations. Diffusion studies were performed through human heat separated epidermis (HHSE) using Franz Diffusion Cells (FDC). Patches provided different fluxes varying from 20.39 ± 7.09…
Compared effects of synthetic and natural bile acid surfactant on xenobiotic absorption. II. Studies with sodium glycocholate to confirm a hypothesis
Abstract The effects of sodium glycocholate (SGC) on the intestinal absorption of drug-related xeriobiotics are investigated, on the basis of previously established absorption/partition relationships. Six phenylalkylcarboxylic acids, closely related to nonsteroid anti-inflammatory drugs in structure and constituting a true homologous series, were used as test compounds through an in situ rat gut technique, using the whole colon as nonspecialized absorption membrane model. Whereas the synthetic surfactants (i.e., polysorbates and laurylsulphates) at the critical micelle concentration have been shown to disrupt the aqueous boundary layer adjacent to the membrane, SGC does not; in contrast, it…
Pharmacokinetics, bioavailability and absorption of flumequine in the rat.
Abstract The study demonstrates that the oral extent of bioavailability of flumequine in the rat, relative to the intravenous injection, is complete (0.94±0.04) and not significantly different from that found by the intraduodenal route (0.95±0.04). The rate of oral bioavailability, however, is slow ( k a =1.20±0.07 h −1 ; T max =2.0 h), but enough to maintain plasma levels above the minimal inhibitory concentration of the most common pathogens for an extended period of time (about 10 h). The reason for the oral absorption slowness could be a slow gastric emptying, an adsorption to the gastric mucosae, a precipitation in the gastric medium or any other feature concerning the stomach as the i…