The modern drug alaptide, synthetic dipeptide, shows regenerative effects and effects on the epitelisation process. A commercial product consisting of 1% alaptide hydrophilic cream is authorised for use in veterinary practice. This study focuses on the formulation of alaptide into semi-synthetic polymer-based hydrogels. The aim of the present study is to prepare hydrogels and to evaluate the liberation of alaptide from hydrogels. The hydrogels were prepared on the basis of three gel-producing substances: methylcellulose, hydroxyethylcellulose and hydroxypropylcellulose. To enhance the drug release from hydrogel humectants, glycerol, propylene glycol and ethanol in various concentrations were evaluated. The permeation of the alaptide from gels into the acceptor solution was evaluated with the use of the permeable membrane neprophane. The amount of drug released from prepared hydrogels was determined spectrophotometrically. Hydrogels with optimal alaptide liberation properties were subjected to the study of rheological properties in the next phase. The optimal composition of hydrogel as established in this study was 1% alaptide + 3% hydroxyethylcellulose with the addition of 10% glycerol as humectant. Due to the advantageous properties of hydrogels in wounds, alaptide could be incorporated into a hydrogel base for use in veterinary medicine. , gel-producing substance, humectant, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose Hydrogel research increased significantly in the last decades; due to their properties, hydrogels are widely used as suitable bases of preparations in human and veterinary medicine. The properties of hydrophilic gels, or hydrogels, are significantly different from those of ointments and creams. Hydrogels are usually formed by hydrophilic polymers which under certain conditions and polymer concentrations create a gel with a high percentage of water. They can additionally contain glycerol or propylene glycol as humectants and ethanol as an antimicrobial agent. Hydrogels create a smooth film that adheres well, can be removed easily and exhibits a cooling effect. The active substances have been dispersed in hydrogels (dissolved, suspended or emulsified). The base with the incorporated active ingredient must have suitable properties, especially biocompatibility and chemical, microbiological and physical stability (Bronaugh and Maibach 2001). EpitelisationPeptide drugs are becoming an essential part of modern therapy. Beside their therapeutic effect they can perform the function of another non-peptide drug carrier. Their reactions on changes of the pH milieu, biocompatibility, thermosensitivity and good mechanical properties have been reported (Galaev and Mattiasson 2008).Alaptide is spirocyclic synthetic dipeptide, chemically prolyl-leucyl-glycine amide derivative (Nedvidková et al. 1994). Due to its positive influence on regenerative processes in various skin diseases it can be used in veterinary medicine. For a long time it has been used as a commercial 1% hydrophilic ...
In this open-label, laboratory-blinded, 2-way single dose study in 24 volunteers of both sexes we found that (1) nabumetone reaches mean Cmax ± SD of 0.56 ± 0.20 mg·L at mean tmax of 8.63 ± 7.05 hours, and mean area under the curve (AUC)last of 18.07 ± 7.19 h·mg·L; (2) there are no statistically significant differences between both sexes in pharmacokinetics of nabumetone; (3) 6-methoxy-2-naphthylacetic acid (6-MNA) reaches higher AUClast in men compared with women (mean ± SD, 721.23 ± 185.53 h·mg·L and 545.27 ± 97.69 h·mg·L, respectively; P = 0.013); (4) there is lower 6-MNA clearance in men (0.65 ± 0.22 L·h) in comparison with women (0.88 ± 0.18 L·h, P = 0.019), (5) intersubject variability of nabumetone and 6-MNA is between 35%-45% and 10%-30% for all assessed pharmacokinetics parameters (AUClast, Cmax, partial AUC values); (6) intrasubject variability (ISCV) for AUClast is low, 15.59% and 6.40% for nabumetone and 6-MNA, respectively, (7) ISCV for Cmax is 13.66% and 5.42% for nabumetone and 6-MNA, respectively. Nabumetone thus belongs to compounds with low to moderate ISCV and therefore this product is expected to produce consistent effects in clinical practice.
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