Preparation and in vitro evaluation of thermosensitive and mucoadhesive hydrogels for intranasal delivery of phenobarbital sodium

Background: Recently, intranasal administration has been suggested as a potential direct route to transport pharmaceuticals into the brain through the olfactory and trigeminal nerves, bypassing the blood–brain barrier. Materials & methods: The nasal hydrogels were prepared by a cold method using pluronic F-12 and chitosan. Results: All the selected formulations were gelled at 30°C. The gelation time varied from 5 to 10 min. The mucoadhesive strength was adequate to provide prolonged mucosal adhesion. The formulations exhibited good drug content after stability period of 3 months. The permeability studies revealed a high permeation of the drug through the surgically removed nasal tissue. Conclusion: The results suggest that the obtained hydrogels might be suitable candidates for the nasal delivery of phenobarbital sodium.

Prevalence of Gingival Hyperplasia Induced by Anticonvulsants: A Systematic Review

Objective: Gingival hyperplasia (GH) is one of the side effects of anticonvulsant drugs. The aim of this study was to verify the prevalence of GH associated with the use of anticonvulsant, through a systematic review. Material and Methods: Systematic search was done at databases Pubmed and Embase between January 1984 and March of 2020 for identification of articles addressing the prevalence of GH associated with the use of anticonvulsant drugs. The methodological index for non-randomized studies (MINORS) was independently assessed for quality in the selected papers. Results: The search identified 4.471 references. Nine articles were selected and evaluated 632 participants. All of the studies included in the systematic review showed a low risk of bias. The anticonvulsants used by patients were carbamazepine, ethosuximide, phenytoin, primidone, phenobarbital, sodium valproate. The studies showed a correlation between different types of anticonvulsants and GH prevalence, with a range from 0% to 73%. Among the anticonvulsants used, phenytoin showed the greatest incidence of GH, varying between 15.61% and 73% in patients. Conclusion: In the analysis of the results obtained in the literature, it is possible to notice that the great majority of studies presented incidence of GH associated with anticonvulsant use. However, further studies are necessary to understand the anticonvulsant action mechanism inducing GH, as well as the prevention forms, given that GH is a significant side effect. KEYWORDS Anticonvulsants; Gingival hyperplasia; Prevalence.

FAST DISSOLVING SUBLINGUAL PATCH OF PHENOBARBITAL SODIUM: FORMULATION AND IN VITRO EVALUATION

Objective: To formulate and characterize. Phenobarbital sodium loaded sublingual patch using biodegradable, mucoadhesive, fast-dissolving natural polymer pullulan for immediate management of epileptic seizures. Methods: Phenobarbital sodium loaded sublingual patches were prepared by the solvent casting method and were subjected to various physicochemical evaluation parameters to find the optimized sublingual patch. The in vitro drug release study and kinetic model of the optimized formulation was also carried out. The stability study of the optimized Phenobarbital sodium loaded sublingual patch was also done. Results: From in vitro drug release study, it was found that Phenobarbital sodium loaded sublingual patch (S4) exhibited a maximum drug release of 96.24±1.27% at the end of 60 min compared to other formulations indicating a faster drug release from the formulation with release kinetics as Higuchi diffusion model. In fact, a notable release data was obtained between 0.5 to 8 min by all formulations, specifically S4 formulation (20.84±1.97% and 77.22±2.41% drug release at the end of 0.5 min and 8 min respectively) showed a better percentage release profile in comparison with other formulations. Such a trend is vital to deliver the drug at a faster rate to promote immediate effect for managing the fatal and complicated seizure. Considering the physicochemical property and in vitro drug release data, S4 formulation was regarded as an optimized one. The stability study also confirmed that S4 formulation is stable at refrigeration conditions. Conclusion: The formulated Phenobarbital sodium loaded sublingual patch is an effective drug delivery carrier which enables faster drug release to manage epileptic seizure.

Synthesis of new 6-hydroxypyrimidine-4(3Н)-onе derivatives

In this paper, 6-hydroxypyrimidine-4 (3Н)-one derivatives are considered as promising syntones for the creation of new biologically active substances. This is useful since the pyrimidine fragment is a structural component of nucleic acid bases (cytosine, thymine, uracil), uric and orotic acids, coenzymes (flavins and xanthins), a number of vitamins (folic acid, thiamine, pyridoxine, riboflavin). It is worth noting that the pharmaceutical market is widely represented with antitumor (methotrexate, imatinib, tegafur); antiviral (stavudine, zalcitabine, lamivudine, zidovudine, acyclovir, idoxuridine); immunostimulatory (isophone) and sedative drugs (phenobarbital, sodium ethaminal) based on compounds including the pyrimidine cycle. The purpose of the present work is to develop a method for producing new 2,3-diphenyl-5-(alkyl/ phenyl)-6-hydroxypyrimidin-4(3Н)-ones, proving their structure and individuality by NMR spectroscopy and mass spectrometry, elemental analysis and thin-layer chromatography. As a method of producing new 6-hydroxypyrimidin-4(3Н)-ones, a method of condensing N-phenyl-benzenecarboxymidamide with 2-substituted propanedioyldichlorides in the medium of an aprotic non-polar solvent – o-xylene is proposed. The desired products are isolated from the reaction mass using solvent distillation and a reprecipitation method. It was found that maximum yields are achieved with constant stirring of a suspension of N-phenylbenzenecarboxymidamide with a solution of 2-substituted propanedioyl dichloride in o-xylene and further heating of the reaction mass at 144 °C for 4 hours. The individuality of the synthesized compounds was confirmed by thin layer chromatography on Sorbfil® plates in the methanol-dichloroethane (1:9) system, and their structure was proved using modern physicochemical analysis methods: proton magnetic resonance spectroscopy, NMR С13 spectroscopy, mass spectroscopy and elemental analysis.