Buflomedil Hydrochloride Research Articles

Controlled simultaneous iontophoresis of buflomedil hydrochloride and dexamethasone sodium phosphate to the mucosa for oral submucous fibrosis

A novel concentric experimental set-up was used to investigate short-duration topical co-iontophoresis of cationic buflomedil hydrochloride (BUF) and anionic dexamethasone phosphate (DEX-P) to the oral mucosa. A constant current of 3.0 mA (0.6 mA/cm2 for BUF and 1.95 mA/cm2 for DEX-P) was applied to porcine esophageal mucosa for 5, 10 and 20 min. Iontophoresis for only 5 min increased total delivery of BUF from 29.8 ± 5.1 nmol/cm2 to 194.3 ± 23.8 nmol/cm2 and DEX-P from 29.4 ± 1.2 nmol/cm2 to 193.3 ± 19.8 nmol/cm2 as compared to passive controls. Quantification of drug between the electrode compartments reported on lateral ion migration. In the absence of current, DEX-P did not migrate laterally; however, iontophoresis for 5 min increased DEX-P delivery >5-fold under the cathodal compartment (its application area) and >8-fold in the adjacent “inter-electrode” area. Similarly, delivery of BUF increased ~6.8-fold under the anodal compartment and ~12.8-fold under the cathode. The results showed that co-iontophoresis enabled the controlled simultaneous delivery of BUF and DEX-P achieving therapeutically relevant concentrations after current application for only 5 min. Short duration topical co-iontophoresis of single or multiple therapeutics to the mucosa increases local bioavailability and presents a patient-friendly treatment for diseases of the oral cavity.

Topical iontophoresis of buflomedil hydrochloride increases drug bioavailability in the mucosa: A targeted approach to treat oral submucous fibrosis.

The aim was to investigate the effect of constant current iontophoresis on the delivery and biodistribution of buflomedil hydrochloride (BUF) in the buccal mucosa. Quantification was by UHPLC-MS/MS; in addition to total delivery, the amounts present in the epithelia and the lamina propria (the target tissue) were also determined. Two-compartment vertical diffusion cells were used to investigate the effect of current density (0.5, 1 and 2 mA/cm2), application time (5, 10 and 20 min) and concentration (5, 10 and 20 mM) on iontophoretic delivery of BUF from aqueous solutions. In contrast to passive delivery, iontophoresis for 10 min at 1 mA/cm2 resulted in statistically equivalent transport from a 20 mM solution and a 2% HEC hydrogel (with equivalent BUF loading; 20 µmol). BUF delivery from the hydrogel using diffusion cells and a new coplanar "side-by-side" set-up was statistically equivalent (304.2 ± 28.9 and 278.2 ± 40.3 µg/cm2) - passive delivery was also similar. Iontophoresis (10 min at 1 mA/cm2) using a thin film (20 µmol BUF) was superior to the passive control (323.3 ± 5.9 and 24.8 ± 5.9 µg/cm2). Concentrations in the LP were ~700-fold > IC50 to block collagen production, potentially providing a new therapeutic strategy for oral submucous fibrosis.

Facile preparation of acrylamide grafted locust bean gum-poly(vinyl alcohol) interpenetrating polymer network microspheres for controlled oral drug delivery

Hybridization of natural and synthetic polymers is used to improve the physicochemical stability, swelling and drug release pattern of the respective materials in biological condition. In present study, a biodegradable, biocompatible and stable interpenetrating polymer network (IPN) of acrylamide grafted locust bean gum (Am-g-LBG) and poly(vinyl alcohol) (PVA) was developed by emulsion crosslinking method for spatial and temporal drug delivery. The IPN microspheres were prepared with the help of glutaraldehyde as a crosslinker for controlled oral delivery of buflomedil hydrochloride. The formulation parameters were optimized in terms of different gum:PVA ratio, crosslinker amount and drug loading. The microspheres were evaluated for their drug entrapment efficiency, particle size, swelling, SEM, FTIR, NMR, DSC, XRD and in vitro drug release profile. The particles showed well controlled release characteristics and continued to drug release following diffusion controlled release pattern. The drug release was for prolong time without collapsing the particle matrix. Thus, IPN microspheres based delivery system can be a better approach for controlled delivery of highly water soluble drugs like buflomedil hydrochloride.

Skin permeation of buflomedil form adhesive matrix patches

The main objective of this research work was to fabricate and evaluate adhesive matrix-type transdermal patches of buflomedil hydrochloride, employing different ratios of pressure sensitive adhesives (PSAs) by solvent casting technique. The adhesive matrix-type transdermal patches were evaluated by their in vitro physicochemical properties such as thickness, moisture content, weight variation, drug content uniformity, etc. The effects of PSAs ratio, drug loading, and concentration of permeation enhancer were evaluated thoroughly. Ex vivo skin permeation studies with kinetic modeling of adhesive matrix patches were systematically evaluated. Based on the above observations, the best optimized buflomedil hydrochloride-loaded adhesive matrix-type transdermal patch was further characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction study, and differential scanning calorimetry analyses. Drug containing adhesive matrix patches showed sustained release property without showing any incompatibility in adhesive matrix system. Hence, adhesive matrix-type transdermal patches of buflomedil hydrochloride can be used as a potential carrier for sustained transdermal delivery of hydrophilic drugs like buflomedil hydrochloride.

Preparation and evaluation of a buflomedil hydrochloride niosomal patch for transdermal delivery

Context: Niosomes are the non-ionic surfactant vesicles obtained on hydration of synthetic non-ionic surfactants. These are the promising vehicles for effective transdermal drug delivery.Objective: The present research work was aimed to develop niosomal-based transdermal buflomedil hydrochloride patch containing a stable formulation with improved drug permeation.Materials and methods: Niosomes were prepared by solvent evaporation method using 32 factorial design. All the formulations were evaluated for vesicle size, zeta potential and percent entrapment efficiency. Optimized niosomal and liposomal formulation were loaded into a patch system. All the patches were then characterized for drug–excipient interaction study, scanning electron microscopy, pharmacotechnical properties and in vitro permeation studies.Result: F9 formulation having optimum vesicle size (10.09 ± 1.2 µm), highest zeta potential (−85.4 ± 0.56 mV) and maximum percent entrapment efficiency (97.09 ± 0.11%) was selected as optimized formulation. In case of liposomes, formulation F12 was selected. Patches loaded with niosomes showed 95.12 ± 1.19% cumulative amount of drug permeated as compared to liposomal vesicle-loaded patches which showed 82.21 ± 1.24% and control patches 70.10 ± 1.33%. Discussion: Flux, permeation rate and permeability coefficient were found to be higher in case of niosomal patches as compared to liposomal patches and control patches. Surfactant present in niosomes act as a penetration enhancer which contribute in the permeation enhancement of buflomedil hydrochloride from niosomes.Conclusion: Thus, it was concluded that niosomal vesicles represented to be an efficient and stable vesicular carrier for transdermal delivery of buflomedil hydrochloride.

Comparative bio-safety and in vivo evaluation of native or modified locust bean gum-PVA IPN microspheres

Strategically developed natural polymer-based controlled release multiparticulate drug delivery systems have gained special interest for “spatial placement” and “temporal delivery” of drug molecules. In our earlier study, locust bean gum-poly(vinyl alcohol) interpenetrating polymer network (LBG-PVA IPN), carboxymethylated locust bean gum-poly(vinyl alcohol) interpenetrating polymer network (CMLBG-PVA IPN) and acrylamide grafted locust bean gum-poly(vinyl alcohol) interpenetrating polymer network (Am-g-LBG-PVA IPN) were prepared and characterized. The present study deals with accelerating stability testing, comparative bio-safety and single dose in vivo pharmacokinetic study of all three IPN microspheres for controlled oral delivery of buflomedil hydrochloride (BH). From the stability study, it was observed that the particles were stable throughout the study period. From toxicity and biodegradability study it was proved that the microspheres were safe for internal use and complied with bio-safety criterion. From the in vivo pharmacokinetic study in rabbits, it was observed that the CMLBG-PVA IPN microspheres possessed almost similar Tmax value with BH oral suspension. However, in comparison between the LBG-PVA and Am-g-LBG-PVA IPN microspheres, the later showed well controlled release property than the first in biological condition. Thus, this type of delivery system might be useful to achieve the lofty goals of the controlled release drug delivery.

Application of a high performance liquid chromatography–tandem mass spectrometry method for determination of buflomedil in human plasma for a bioequivalence study

A rapid, simple and sensitive method based on ultra fast liquid chromatography-tandem spectrometry for the determination of buflomedil in human plasma has been developed and validated using carbamazepine as internal standard. After the precipitation of plasma sample with methanol, the analyte and IS were separated on an Ultimate C18 column (5μm, 2.1mm×50mm, MD, USA) with an isocratic mobile phase composed of acetonitrile and 5mM ammonium acetate in water (60:40, v/v) at a flow rate of 0.25ml/min. The analyte and IS were detected with proton adducts at m/z 308.3-237.1 and m/z 237.2-194.2 in positive ion electrospray ionization and multiple reaction monitoring acquisition mode, respectively. The lower limit of quantification of the method was 23.64ng/ml with a linear dynamic range of 23.64-1182ng/ml for buflomedil. The intra- and inter-batch precisions were less than 5.8%. The developed method was successfully applied to a bioequivalence study of two buflomedil hydrochloride preparations (150mg) in 22 healthy Chinese male volunteers.

Carboxymethylation of Locust Bean Gum: Application in Interpenetrating Polymer Network Microspheres for Controlled Drug Delivery

For hydrophilic modification, the sodium carboxymethyl ether of locust bean gum was developed by Williamson synthesis using monochloroacetic acid as the etherifying agent. The modification reaction was optimized in terms of concentration of monochloroacetic acid and sodium hydroxide. The modified gum was evaluated for its degree of substitution, elemental analysis, viscosity, swelling, and contact angle. The etherification of locust bean gum was further confirmed by FTIR, 13C NMR, DSC, and XRD techniques. Acute oral toxicity and biodegradability studies showed that the modified gum was safe enough for internal use. This carboxymethylated gum with poly(vinyl alcohol) was utilized to prepare the interpenetrating polymer network microspheres of buflomedil hydrochloride for controlled drug delivery. The microspheres were evaluated for their drug entrapment efficiency, swelling, and particle size. The microspheres were further characterized by FTIR, 13C NMR, and XRD techniques. The in vitro release study of mi...

Microwave assisted synthesis of acrylamide grafted locust bean gum and its application in drug delivery

Acrylamide grafted copolymer of locust bean gum was prepared by microwave irradiation using ceric ammonium nitrate as redox initiator. The grafting process was optimized in terms of irradiation time, amount of initiator and acrylamide by using constant amount of native locust bean gum. The grafted gum was characterized by Fourier transform infrared spectroscopy (FT-IR), 13C nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), X-ray diffraction study (XRD), differential scanning calorimetry (DSC), elemental analysis, contact angle, viscosity, molecular weight, swelling and biodegradability studies. The grafted gum was found to be biodegradable and non-toxic. It was further used to prepare controlled-release matrix tablet of buflomedil hydrochloride. The in vitro release profile of the tablet showed the rate controlling property of acrylamide grafted locust bean gum was similar to that of hydroxypropyl methylcellulose (HPMC-K15M).

Interpenetrating polymer network of locust bean gum-poly (vinyl alcohol) for controlled release drug delivery

A novel interpenetrating polymer network (IPN) microspheres of locust bean gum (LBG) and poly (vinyl alcohol) (PVA) was developed for oral controlled release of buflomedil hydrochloride (BH) by emulsion crosslinking method using glutaraldehyde as crosslinker. The effects of gum–polymer ratio, concentration of crosslinker and internal phase viscosity were evaluated thoroughly. Drug entrapment efficiency, particle size distribution, swelling property and in vitro release characteristics with kinetic modelling of microspheres were evaluated. The microspheres were characterised by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), solid state C13 NMR, X-ray diffraction study (XRD) and differential scanning colorimetry (DSC). The microspheres showed control release property without showing any incompatibility in IPN device. Hence, IPN microspheres of LBG and PVA can be used as a potential carrier for controlled oral delivery of highly water soluble drugs like BH.

Investigation on Interaction of Buflomedil Hydrochloride with Trypsin: A Spectroscopic Analysis

Investigation on Interaction of Buflomedil Hydrochloride with Trypsin: A Spectroscopic Analysis

Protective Effect of Buflomedil in a Rat Model of Moderate Cerebral Ischemia

Buflomedil hydrochloride (CAS 55837-25-7) is a vasoactive drug with a variety of pharmacodynamic properties. Although a number of studies have been carried out to verify the beneficial effect of buflomedil in ischemic peripheral conditions, few data are reported to justify the efficacious employment of buflomedil in the treatment of cerebrovascular diseases. The aim of the present study was to better investigate the neuroprotective effect of buflomedil in normal pentobarbital-anaesthetized rats subjected to transient bilateral common artery occlusion (BCO) for 20 min. Buflomedil hydrochloride (10 mg/kg) was administered by slow intravenous infusion (90 min), starting 1 h after the onset of ischemia. The rats were sacrificed 48 h after carotid clamping. BCO caused dramatic death of hippocampal CA1 pyramidal neurons, and a significant increase in circulating levels of neuron-specific enolase (NSE) and lactate. Treatment with buflomedil attenuated ischemia-induced histological loss and damage of CA1 pyramidal cells. Furthermore, in ischemic rats, the drug restored blood lactate concentrations and serum NSE concentrations to near normal levels. These data clearly demonstrate that buflomedil is able to protect brain neurons against damage following moderate global cerebral ischemia. One could speculate that this protective effect could be related to the capability of buflomedil to improve cerebral blood flow and energy metabolism, or to a smooth muscle relaxant effect on cerebral blood vessels.

Facilitated column selection in pharmaceutical analyses using a simple column classification system

In this paper, the performance of a previously developed classification system applied to pharmaceutical chromatographic analyses, is investigated. The separation of seven different drug substances from their respective impurities was studied. The chromatographic procedure for acetylsalicylic acid, clindamycin hydrochloride, buflomedil hydrochloride, chloramphenicol sodium succinate, nimesulide and phenoxymethylpenicillin was performed according to the corresponding European Pharmacopoeia (Ph. Eur.) monograph. The separation of dihydrostreptomycin sulphate was performed according to the literature. It is shown that the column ranking system is a helpful tool in the selection of a suitable column in these analyses.

Sudden sensorineural hearing loss: Prognostic factors

Objectives: Sudden sensorineural hearing loss (SSHL) remains a challenge for the clinician since in the majority of cases no definite cause is recognized. The prognosis regarding the final hearing outcome is quite variable, and treatment is mainly based on the intravenous (IV) corticosteroid administration. Various prognostic factors have been reported in the literature: age, tinnitus, electronystagmographic (ENG) findings, hearing level, shape of audiogram, brainstem evoked response audiometry (BSER) findings, and time of initiation of treatment in the final hearing outcome. The aim of the present study was to assess the prognostic significance of demographic, epidemiologic, neurootologic, otologic, and audiometric factors with regard to the hearing outcome of patients with SSHL. Methods: The present study assessed the hearing outcome in 114 patients with SSHL who received the following treatment: Prednisolone IV 1 mg/kg/day for 10 days divided in 3 doses gradually tapered for 5 days, Acyclovir 4 g/day for 5 days divided in 5 doses, Buflomedil hydrochloride 300 mg IV divided in 3 doses for 10 days, Ranitidine IV during steroid treatment. They all had a 12-month follow-up of pure tone and BSER audiometry. Results: The statistical analysis revealed that older age, ENG findings, flat/descending shapes, or total deafness in the initial audiogram, late identification of wave V during the follow-up, worse initial PTA thresholds, and delayed patients’ presentation were significantly correlated to poorer hearing outcome. Conclusions: The present study revealed that there are certain factors that affect prognosis in SSHL. This is very important in counseling patients and may affect current clinical practice.

Investigation on False Peak Phenomena in On‐line Sweeping Technique in MEKC

AbstractIn this paper, several {actors that could lead to the appearance of false peak were investigated by using on‐line sample sweeping technique under different experimental conditions. The tested analytes were buflomedil hydrochloride, ephedrine hydrochloride, benzyl alcohol, vanillin, p‐hydroxybenzaldehyde and m‐methylphenol. Results showed mat among the six compounds, three of them, i.e., buflomedil hydrochloride, ephedrine hydrochloride and benzyl alcohol will cause false peaks to appear when sample injection time is long, sodium dodecyl sulfate (SDS) concentration is high and there is pH gradient between cathode and anode. In order to avoid the appearance of false peak, the pH gradient should be avoided.

Assessment of collateral perfusion: a pharmacodynamic study with buflomedil hydrochloride.

The aim of the study was to assess the influence of Buflomedil hydrochloride on collateral function. Ten patients with isolated superficial femoral occlusions were investigated twice by duplex sonography with measurement sites at the common femoral artery (CF) and the popliteal artery (PA). After the second scan 200 mg of Buflomedil hydrochloride were infused; the infusion was followed by a third duplex examination. Endpoints assessed included the arterial diameter (D(CF), D(PA)), the systolic peak velocity (Vmax), the mean velocity of the maximum envelope (Vmean m.e.), the intensity weighted time average mean velocity (Vmean i.w.), the maximum reverse flow velocity (Vrev), the end-diastolic velocity (Venddiast), the calculated volume flow (Q), the pulsatility and the resistance indices (PI, RI), and PI and RI based segmental damping factors (DF(PI), DF(RI)). For the CF measurement site the infusion of Buflomedil hydrochloride resulted in a significant reduction in Vrev and PI (p<0.05), whereas trends in the opposite direction (increase) were observed for both measures of Vmean and for Q (0.1<p<0.05). No significant changes were reported for the PA measurement site. DF(PI) numerically decreased (0.1<p<0.05). The pattern of changes suggest that Buflomedil hydrochloride induces collateral vasodilation and thus improves collateral function.

Acceleration of wound healing by topical drug delivery via liposomes.

Despite intensive research, impaired wound healing remains a considerable complication. Therefore, topically applied liposome-encapsulated buflomedil hydrochloride was investigated for its ability to improve wound repair in normal (n=16) and ischemic (n=16) skin tissue. Experiments were performed using the wound healing model of the ear of hairless mice. Standardized skin wounds (4.25 mm(2)) were created by circular excision of the epidermal layer and the subcutaneous tissue. Liposomes were applied daily until complete neovascularization of the wound occurred. Tissue regeneration by complete epithelialization and neovascularization of the wound area, microcirculatory parameters, and leukocyte-endothelium interaction were investigated by means of intravital microscopy. Microvascular perfusion was assessed by laser-Doppler flowmetry. Topical application of buflomedil liposomes led to a significantly (P<0.05) accelerated wound closure in both normal (9.6+/-0.7 days) and ischemic (13.4+/-0.1 days) skin tissue compared with animals that were treated with unloaded liposomes (controls; 13.1+/-0.8 days; 15.3+/-0.6 days). Complete neovascularization of the wound was also enhanced (P<0.05) in buflomedil-treated animals (normal tissue 18.8+/-0.4 days; ischemic tissue 19.6+/-0.7 days) compared with controls (20.6+/-0.6 days; 22. 6+/-1.2 days). These data suggest that buflomedil-loaded liposomes might be of beneficial use for clinical wound care.

BUFLOMEDIL HYDROCHLORIDE REDUCES SYSTEMIC ACTIVATION OF POLYMORPHONUCLEAR LEUKOCYTES DURING HYPERDYNAMIC ENDOTOXEMIA

The purpose of the study was to examine the effects of buflomedil hydrochloride (BFL) on the expression of adhesion molecules (beta2-integrins) and oxygen radical production of circulating and emigrated intra-abdominal polymorphonuclear leukocytes (PMNL) in a standardized porcine model of hyperdynamic endotoxemia. A total of 20 anesthetized pigs were randomly assigned to one of the following groups: endotoxin group (endotoxin 5 microg / kg x h, intravenously (i.v.), n = 7), BFL group (BFL (3 mg/kg initial i.v. bolus followed by a continuous infusion (.1 mg / kg x h) and endotoxin 5 microg / kg x h, i.v., n = 7), and control group (NaCl .9%; n = 6). Experiments were terminated at 330 min. Infusion of endotoxin alone resulted in the activation of circulating and emigrated PMNL as evidenced by neutropenia, functional and numerical up-regulation of beta2-integrins, and enhanced oxygen radical production. BFL was able to attenuate functional and numerical up-regulation of beta2-integrins as well as oxygen radical production of circulating and emigrated PMNL. An unexpected decrease in the plasma concentration of BFL during the experiments was associated with an increase in the oxygen radical production of PMNL at the end of the experiments. In addition, BFL attenuated the fall in the intramucosal pH and the increase in plasma concentration of lactate observed in the late phase of endotoxemia. These findings suggest that BFL is able to decrease systemic activation of PMNL and to improve local tissue oxygenation during endotoxemia.

Reduction of Skin Flap Necrosis by Transdermal Application of Buflomedil Bound to Liposomes

The influence of the vasoactive drug buflomedil hydrochloride bound to liposomes (2 mg/ml) was investigated in an arterial pattern skin flap model using the ear of hairless mice. For flap creation, the ear is cut at four-fifths of its base, which leaves the anterior artery as the only feeding vessel of the flap. Liposomes were locally applied daily for 30 minutes up to 5 days after flap creation. Microvascular perfusion in the proximal, central, and distal parts of the flap was measured by laser Doppler flowmetry. The border between perfused and nonperfused tissue was visualized by intravital fluorescence microscopy using fluorescein isothiocyanate (FITC)-labeled dextran (Mr 150,000) for contrast enhancement of microvessels. The area of nonperfused tissue was assessed by digital planimetry. Five days after flap creation the nonperfused area amounted to 23.8 +/- 3.1 percent of total flap surface in treated ears compared with 46.1 +/- 5.6 percent in untreated ears (p < 0.05) of the contralateral side. Additional preoperative treatment for 5 days did not further reduce the area of nonperfused tissue (treated ears, 23.0 +/- 1.3 percent; control ears, 44.6 +/- 5.1 percent). Microvascular perfusion was higher in the postoperatively treated ears in all parts of the flap from day 1 after flap creation until termination of the experiment. Five days after flap creation, perfusion as measured by laser Doppler flowmetry was reduced to 46.0 +/- 10.8 percent in the distal part in control ears compared with 91.9 +/- 8.3 percent (p < 0.05) in treated animals. Additional preoperative treatment for 5 days did not result in further improvement. It is concluded that local application of the vasoactive drug buflomedil docked to liposomes could be of therapeutic use in the treatment of ischemic tissue, including skin flaps.

Visualization of Nutritive Perfusion Following Tourniquet Ischemia in Arterial Pattern Skin Flaps

We present an experimental model that makes it possible to investigate the effects of global ischemia and reperfusion on microvascular perfusion and viability of ill-proportioned (poorly designed) arterial pattern skin flaps in hairless mice. Skin flaps were created on the ears of hairless mice by dissecting two of three nutritional vessel bundles at the ear base. Under these nonischemic conditions, 19 percent of the total flap area went on to necrose (as a result of poor flap design). Global ischemia was induced to the flap tissue for 6 hours with a tourniquet clamp directly after flap incision. The extension of perfused tissue area and flap viability were assessed at the microcirculatory level by intravital video microscopy at 1, 3, 6, and 18 hours and 7 days after reperfusion in animals treated with either normal saline (control) or the vasoactive drug buflomedil hydrochloride (3 mg/kg of body weight per day, i.v., starting 4 hours prior to flap creation and continued at daily intervals until the end of the experiments). In untreated animals (n = 18), 1 hour after clamp release we observed reperfusion of 39.55 percent (38.5/44.9) of total flap area. Reperfusion remained unchanged within the following 5 hours. Within the next 12 hours, reperfused flap area was dramatically reduced to 21.9 percent (15.1/58.4). Seven days thereafter, only 18.8 percent (10.9/42.2) of total flap area remained viable. In contrast, we found in buflomedil-treated animals (n = 18) that 57.3 percent (53.5/62.9) of the total flap tissue was reperfused within the first hour after clamp release (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)