1,721,099 research outputs found
Studio di una polvere nasale per la somministrazione di desmopressina
No full textIn questo lavoro è stata studiata la formulazione di una polvere stabile e biodisponibile adatta alla veicolazione di un principio attivo di natura peptidica (desmopressina) attraverso la via nasale
Effect of excipient composition on the biocompatibility of bupivacaine-containing microparticles at the sciatic nerve
No full textMicroparticulate formulations are often used for experimental prolongation of nerve blockade. Here we examine the effect of excipient composition on the biocompatibility of bupivacaine-containing microparticles. Lipid-protein- sugar particles (LPSPs) composed of 3% (1.3 micron diameter) and 60% (4.7 micron diameter) (w/w) dipalmitoylphosphatidylcholine (DPPC) were produced by spray drying, containing 10% (w/w) bupivacaine. Rat sciatic nerve blocks with 75 mg of particles produced statistically similar durations of sensory nerve block [3% (w/w) DPPC particles: 301 min; 60% (w/w) DPPC particles: 321 min]. Examination of tissues 1 day after injection revealed large particle deposits and acute inflammation in animals that received 60% (w/w) DPPC particles. There were no visible deposits in those that received 3% (w/w) DPPC particles, and microscopic inflammation was reduced. The difference between groups was similar 4 days after injection. Two weeks after injection, there was no particulate mass in either group, and inflammation had largely resolved. In both groups, moderately severe myotoxicity was seen 1 and 4 days after injection but had largely resolved by 2 weeks. In summary, reduction in particles’ DPPC content greatly improved biocompatibility without compromising duration of nerve blockade; the improvement was probably attributable to the enhanced rate of particle resorption
Prolonged duration local anesthesia with lipid-protein-sugar particles containing bupivacaine and dexamethasone
No full textPurpose: Bupivacaine-loaded lipid-protein-sugar particles (LPSPs) can provide prolonged duration local anesthesia. Here, we examine the effect of composition on LPSPs long-term biocompatibility. We also investigate whether the block-prolonging effects of dexamethasone, seen for other local anesthetic-loaded microparticles, apply to LPSPs.
Methods: Male Sprague-Dawley rats were given sciatic nerve blocks with 75 mg of 3 or 60% (w/w) dipalmitoyl-phosphatidylcholine (DPPC) spray-dried LPSPs containing 10% (w/w) bupivacaine and 0, 0.05, or 0.1% (w/w) dexamethasone. Neurobehavioral testing was performed to evaluate block duration. Nerves were harvested to assess biocompatibility.
Results: Dexamethasone-free LPSPs produced sensory blocks lasting 301 ± 56 and 321 ± 127 min for 3 and 60% (w/w) DPPC particles, respectively, with no significant difference. However, large particle debris and acute inflammation were seen in animals receiving the more hydrophobic formulation at 1 and 4 days after injection, whereas only mild inflammation occurred in the 3% DPPC group. When 0.05% (w/w) dexamethasone was added, durations of block increased to 610 ± 182 and 538 ± 222 min, respectively. Higher dexamethasone resulted in no further improvement. Dexamethasone reduced inflammation at day 1 in both groups. In all cases, inflammation was largely resolved by two weeks.
Conclusions: Reduction in DPPC content greatly improved the biocompatibility of bupivacaine-loaded LPSPs, without affecting duration of block. Dexamethasone almost doubled the duration of nerve block, while maintaining particles’ excellent biocompatibility
Strategies in bupivacaine delivery for prolonged duration local anesthesia
No full textLocal anesthesia is intended as all technique that makes a region or part of the body insensitive to pain without loss of consciousness. It is produced by injection of a local anesthetic drug (LAs) in solution into the epidural or subarachnoid spaces or near specific nerves (nerve block). Clinically, prolonged duration of anesthesia and limited systemic and local toxicity are desirable. These goals may be achieved by means of slow release formulations that maintain active drug concentrations at the injection site for longer periods of time. In addition, local anesthetics can be given in association with non-anesthetic drugs that were shown to have a synergistic effect with LAs.
Here, the performances of three different formulations containing bupivacaine are investigated in vivo (rats) with respect to both in vivo sciatic nerve block and tissue reaction. The aim of this research was to develop an injectable formulation for bupivacaine administration able to induce nerve block lasting from several hours to days or weeks.
At the end of the work, different durations of block were obtained with the three formulations investigated and local tissue reaction at injection site was highly dependent on the system’s composition and degradation profile. Nevertheless, all these systems may be useful to provide prolonged duration local anesthesia adequate to various clinical conditions
Spray therapeutic paint for topical treatment of orf virus skin infections in breeding sheep
No full textA new product in the form of a therapeutic paint was developed for topical treatment of orf virus skin infection in sheep. The formulation combines the potent antiviral cidofovir and the wound-healing properties of sucralfate gel
Efficacy and biocompatibility of bupivacaine-loaded lipid-protein-sugar particles for prolonged duration local anesthesia
No full textPurpose. To investigate whether decreasing the phospholipidic fraction in lipid-protein-sugar particles (LPSPs), designed to achieve prolonged duration local anesthesia, can reduce tissue reaction without compromising the duration of nerve block.
Methods. Bupivacaine-loaded LPSPs were prepared by spray drying an ethanol:water mixture containing albumin, α-lactose, dipalmitoyl-phosphatidylcholine (DPPC, 3% or 60% w/w) and bupivacaine. Drug loading was assessed. Duration of block was measured in rats following sciatic nerve injection. One, 4 and 14 days after the injection, nerves were harvested for histology, together with adherent tissues. Results. 60% and 3% DPPC particles had 7.18 ± 0.47% and 7.21 ± 0.94% bupivacaine loading, respectively. Sensory and motor block from 3% DPPC lasted 301 ± 56 minutes and 412 ± 173 minutes. Corresponding data for 60% DPPC particles were 321 ± 127 and 513 ± 216 minutes with no statistically significant difference between formulations. On gross dissection, pockets of particles were not detectable in any animal receiving 3% DPPC particles. However, they were detected in all animals receiving 60% DPPC particles 1 day after injection, 2 of 4 rats at 4 days, none at 14 days. All animals showed an acute inflammatory response with neutrophils at 1 day after injection; at 4 days, the rats receiving the 60% DPPC particles still showed acute inflammation, while 3% DPPC particles led to a milder tissue reaction with more mononuclear cells. At 14 days, both groups showed a mild mononuclear reaction. Conclusion. The two formulations containing the same loading of bupivacaine but different amounts of DPPC demonstrated equivalent durations of block. The 3% DPPC formulation had a shorter tissue dwell time and milder tissue reaction than the 60% formulation
Drug binding to human serum heme-albumin impairs allosterically peroxynitrite detoxification
No full textThe heme endows human serum albumin (HSA) with reactivity and spectroscopic properties similar to those of hemoglobin
and myoglobin. Here, warfarin and ibuprofen, the prototype ligands of Sudlow′s sites I and II, respectively, are reported to
modulate allosterically peroxynitrite isomerization to nitrate by ferric heme-albumin (HSA-heme-Fe(III))
A new 5-methoxypsoralen formulation for the topical treatment of psoriasis
No full textPurpose. The oral treatment with 5-methoxypsoralen (5-MOP) is mandatory in the case of diffused psoriasis, but can be replaced by topical treatment when the number and extension of psoriatic plaques allow it. The aim of this work was to realize a new 5-MOP topical formulation characterized by high skin permeability. Methods. The system realized was a lotion (5-MOP content 0.06 % and 0.13 % w/w), containing lecithin and cholesterol. The permeation of 5-MOP from the lotion was studied "in vitro" through rabbit ear skin, using Franz diffusion cells. Since the psoralen has very low water solubility (3 mcg/ml at 25 °C), the receptor solution contained beta-cyclodextrin in order to guarantee sink conditions. Results. The results obtained show that the lotion was able to improve the permeation characteristics of 5-MOP compared to other topical formulations (such as the water solution or the gels currently used in therapy). In particular, compared to the gel formulation, the 5-MOP flux was doubled and the lag time was reduced from 1 h to a few minutes. Both can be an advantage in the practical application, since can shorten the application time before UV irradiation. The increase of drug concentration from 0.06 to 0.13 % did not modify drug permeation. Conclusion. In conclusion, the new formulation shows very good permeation characteristics and can constitute a promising alternative to the existing formulations in the topical treatment of psoriasis
Soft agglomerates containing microencapsulated levothyroxine for buccal or oral delivery
No full textThe aim of this work was to prepare a new levothyroxine solid dosage form potentially suitable for buccal administration, obtained by agglomeration of spray-dried microparticles containing the thyroid hormone T4
In vitro comparison of four anti-inflammatory topical medications
No full textMeasurement of in vitro release and diffusion across a barrier (artificial or biological) of the active ingredient sodium diclofenac from topical products (two originators and the corresponding generics) was carried out.
Diclofenac release and availability appeared to be influenced by formulation characteristics, although the observed differences were reduced when skin was used instead of the artificial barrier. The information collected may be useful for the pharmacist when advising patients in the field of anti-inflammatory topical medications
- …
