Release Of Phenytoin Research Articles

Antiepileptic drug-loaded and multifunctional iron oxide@silica@gelatin nanoparticles for acid-triggered drug delivery

The current study developed an innovative design for the production of smart multifunctional core-double shell superparamagnetic nanoparticles (NPs) with a focus on the development of a pH-responsive drug delivery system tailored for the controlled release of Phenytoin, accompanied by real-time monitoring capabilities. In this regard, the ultra-small superparamagnetic iron oxide@silica NPs (IO@Si MNPs) were synthesized and then coated with a layer of gelatin containing Phenytoin as an antiepileptic drug. The precise saturation magnetization value for the resultant NPs was established at 26 emu g-1. The polymeric shell showed a pH-sensitive behavior with the capacity to regulate the release of encapsulated drug under neutral pH conditions, simultaneously, releasing more amount of the drug in a simulated tumorous-epileptic acidic condition. The NPs showed an average size of 41.04 nm, which is in the desired size range facilitating entry through the blood–brain barrier. The values of drug loading and encapsulation efficiency were determined to be 2.01 and 10.05%, respectively. Moreover, kinetic studies revealed a Fickian diffusion process of Phenytoin release, and diffusional exponent values based on the Korsmeyer-Peppas equation were achieved at pH 7.4 and pH 6.3. The synthesized NPs did not show any cytotoxicity. Consequently, this new design offers a faster release of PHT at the site of a tumor in response to a change in pH, which is essential to prevent epileptic attacks.

Fabrication of Bio-Nanocomposite Based on HNT-Methionine for Controlled Release of Phenytoin.

In this study, a novel promising approach for the fabrication of Halloysite nanotube (HNT) nanocomposites, based on the amino acid named Methionine (Met), was investigated. For this purpose, Met layered on the outer silane functionalized surface of HNT for controlled release of Phenytoin sodium (PHT). The resulting nanocomposite (MNT-g-Met) was characterized by FTIR, XRD, Zeta potential, TGA, TEM and FE-SEM. The FT-IR results showed APTES and Met peaks, which proved the modification of the HNTs. The zeta-potential results showed the interaction between APTES (+53.30) and Met (+38.80) on the HNTs (−30.92). The FE-SEM micrographs have displayed the grafting of Met on the modified HNTs due to the nanotube conversion to a rough and indistinguishable form. The amount of encapsulation efficiency (EE) and loading efficiency (LE) of MNT-g-Met was 74.48% and 37.24%, while pure HNT was 57.5%, and 28.75%, respectively. In-vitro studies showed that HNT had a burst release (70% in 6 h) in phosphate buffer while MNT-g-Met has more controlled release profile (30.05 in 6 h) and it was found to be fitted with the Korsmeyer-Peppas model. Due to the loading efficiency and controlled release profile, the nanocomposite promote a good potential for drug delivery of PHT.

Polymeric nanocapsules as a binder system for fluidized bed granules: Influence on particle growth behavior, flow, compaction properties, and drug release

The use of polymeric nanocapsules as a binder system to produce fluidized bed granules with improved in vivo bioavailability has recently been reported. This study evaluated how the nanocapsules influence the growth behavior of the fluidized bed granules. Phenytoin-loaded nanocapsules were sprayed top-down sprayed onto a substrate. A linear correlation (r = 0.9863) between the volume of the sprayed suspension and the mean particle size was found. Well-defined solid bridges were observed in the granule structure by Scanning Electron Microscopy. The surface area coverage of the granules was 0.145%, suggesting arrangement of the nanocapsules on the surface and in the solid bridges, corroborating the Raman images. The granules had a cohesive nature without powder segregation. The use of nanocapsules promotes the controlled release of phenytoin, and these data contribute to the understanding of the role of polymeric nanocapsules as a binder in fluid bed granulation to produce granules for posterior tableting or capsule filling processes.

Exploration of Inbuilt Novel Properties as Bioretardant Cum Stabilizer of Isolated Biopolymer from Fragaria ananassa in Delivery of Nanosized Phenytoin.

The research aims to develop bionanosuspension using a biopolymer isolated from Fragaria ananassa fruit that constitutes potential and natural polymeric properties. At first, the biomaterial was isolated from the natural fruit pulp of Fragaria ananassa by an economical method of isolation. The model drug was nanosized by a novel sonication method. The isolated biopolymer was characterized for its polymeric properties, and its potential capabilities were evaluated in the delivery of nanosized phenytoin. The isolated biopolymer was characterized for DSC, FTIR, NMR, mass, and scanning electron microscopy. The isolated biomaterial was used for the preparation of phenytoin-loaded bionanosuspension with other excipients. The bionanoparticles were also characterized by different analytical testing such as FTIR, DSC, and SEM to confirm any interaction between model drug and biopolymer.The prepared bionanoparticles showed the release of phenytoin in a sustained manner over 36 hours. The release kinetic study was done using the BIT-SOFT 1.12 software and other parameters such as t50%, t80%, and r2 were calculated. The formulation PFr6 was considered best having t50% in 18.22 hours and t80% in 29.62 h with an r2 value of 0.9793. This formulation showed up to 87.89% drug release within 36 hours. The prepared bio-nanosuspension was found to be stable and in a well-dispersed state. The dried bionanosuspension evaluation revealed no interaction between model drug and biopolymer without any loss of characteristic peaks. Therefore, the isolated biopolymer can be safely used to prepare stable bionanosuspension loaded with nanosized phenytoin.

A Smart Approach for Delivery of Nanosized Phenytoin using Biomaterial Isolated from Fragaria ananassa

Objectives: The bionanosuspension was prepared by using the isolated biopolymer from Fragaria ananassa fruit which serve as a potential, natural polymeric nature biomaterial. The isolated biomaterial was used for the preparation of nanosized phenytoin loaded bionanoparticles in the form of bionanosuspension. The isolated biopolymer was characterized for its polymeric properties and its potentiality was evaluated in the delivery of nanosized phenytoin. Materials and Methods: The isolated biopolymer from Fragaria ananassa was used for the formulation of phenytoin loaded bionanosuspension. The sonication method was used for the preparation of bionanosuspension having bionanoparticles in nano range loaded with nanosized phenytoin. The accurate quantity of phenytoin and isolated biopolymer was mixed with other excipients like dextrose as nanosizent, polyvinyl alcohol, sodium benzoate with double distilled water and then sonicated in bath sonicator for 15 cycles (1cycle=3min). Results: The isolated biopolymer was characterized for DSC, FTIR, NMR, Mass and Zeta particle size analysis. The obtained results confirm its polymeric nature in different analysis. The prepared bionanoparticles showed the release of phenytoin in sustained manner over 36 hr. The release kinetic study was done by using the BIT-SOFT 1.12 software and t50% and t80%, r2 were calculated. The formulation PF4 was found to be the best formulation having t50% of 17 hr and t80% of 28 hr with r2 value of 0.9912. The best formulation PF4 showed up to 90.64% drug release over 36 hr. According to the release kinetic study the best fit model was found to be Korsmeyer- Peppas and the mechanism of drug release was found to be anomalous transport. Conclusion: Thus the isolated biopolymer from fruit pulp of Fragaria ananassa can be safely used for the preparation of nanosized phenytoin loaded bionanoparticles in the delivery of phenytoin in significant amount for the treatment of epilepsy.

Chitosan hydrogels containing nanoencapsulated phenytoin for cutaneous use: Skin permeation/penetration and efficacy in wound healing

Although phenytoin is an antiepileptic drug used in the oral treatment of epilepsy, its off-label use as a cutaneous healing agent has been studied in recent years due to the frequent reports of gingival hyperplasia after oral administration. However, the cutaneous topical application of phenytoin should prevent percutaneous skin permeation. Therefore, the aim of this study was to evaluate the in vitro skin permeation/retention and in vivo effects of nanocapsules and nanoemulsions loaded with phenytoin and formulated as chitosan hydrogels on the healing process of cutaneous wounds in rats. The hydrogels had adequate pH values (4.9–5.6) for skin application, drug content of 0.025% (w/w), and non-Newtonian pseudoplastic rheological behaviour. Hydrogels containing nanocapsules and nanoemulsions enabled improved controlled release of phenytoin and adhesion to skin, compared with hydrogels containing non-encapsulated phenytoin. In vitro skin permeation studies showed that phenytoin permeation to the receptor compartment, and consequently the risk of systemic absorption, may be reduced by nanoencapsulation without any change in the in vivo performance of phenytoin in the wound healing process in rats.

Topical application of phenytoin or nifedipine-loaded PLGA microspheres promotes periodontal regeneration in vivo

ObjectivesGingival recession and alveolar bone loss are common manifestations of periodontitis. Periodontal regeneration is the ideal strategy for rehabilitating periodontal tissue defects and preventing tooth loss. The present study examined whether localized, topical application of gingival overgrowth-inducing drugs, phenytoin, nifedipine or cyclosporine, induces periodontal regeneration. MethodsPolylactic-co-glycolic acid (PLGA) was used as the carrier for preparation of phenytoin, nifedipine or cyclosporine-loaded PLGA microspheres, using an oil-in-water emulsification technique. The drug-loaded microspheres were delivered to periodontal defects created on alveolar ridges mesial to the first maxillary molars of Sprague-Dawley rats. After eight weeks, the operation area in each rat, including the maxillary molars and periodontal tissues, was harvested and evaluated by micro-computed tomography, histochemical and immunohistochemical analyses. ResultsPhysical parameters representative of periodontal regeneration, including the length of new alveolar bone (p < 0.01) and the area of new alveolar bone (p < 0.01) were significantly improved in the phenytoin group. Compared to other groups, the phenytoin group demonstrated increased expression of COL-1, VEGF-A, osteoblast and osteoclast markers (BMP-2, TGF-β1, OCN and TRAP staining), as well as decreased expression of MMP-8. ConclusionsResults of the present study provided new evidence that localized, controlled release of phenytoin confers therapeutic benefits toward gingival recession and alveolar bone loss. Phenytoin appears to be a promising drug that promotes periodontal regeneration.

Synthesis of new molecularly imprinted polymer via reversible addition fragmentation transfer polymerization as a drug delivery system

Living free-radical polymerization via reversible addition fragmentation chain transfer (RAFT) polymerization in presence of a chain transfer agent (CTA) was used to synthesize a new series of molecularly imprinted polymers (MIPs) for phenytoin as template in order to drug delivery carrier. MIPs were synthetized based on acrylamide (AAm) and ethylene glycol dimethacrylate (EGDMA) by precipitation polymerization method with different cross-linker content (≤83%). To distinguish effect of RAFT polymerization on the morphological and binding characterization of MIPs, polymer synthesis was also performed via traditional radical polymerization (MIP-TRP) in absence of CTA. Morphological, structural and thermal properties of polymers were studied by SEM, FT-IR, XPS and TGA analyses. RAFT polymerization led to ∼10% increasing in capacity of MIPs. Also, it was resulted in increasing of apparent total number of binding site (NT) of MIPs from 18.32 mg g−1 by TRP to 26.07 mg g−1 by RAFT. In MIP with lower cross-linker content (50%), living polymerization showed increasing effect on the imprinting factor (IF) and relative selectivity coefficients for analogue drug. The IF of MIP-TRP increased from 1.1 to 1.8 by MIP synthesis in presence CTA (MIP-RAFT). Results showed that drug loading on MIPs extended phenytoin release from 12 h (unloaded drug) to 40–140 h and MIP-RAFT presented more delayed release profile than MIP-TRP.

LIPID MICROEMULSION-BASED HYDROGELS FOR EFFECTIVE TOPICAL DELIVERY OF PHENYTOIN

Objective: Microemulsion is a promising drug delivery vehicle for lipophilic drugs but its acceptability for topical application is limited to its very low viscosity. The aim of the present study was to develop and characterize lipid microemulsion hydrogel as a topical drug carrier for phenytoin.Methods: Lipid oil-in-water (O/W) emulsions were formulated from palm kernel oil (PKO), coconut kernel oil (CKO) and soybean oil (SBO), and their blends using phase inversion temperature method. Stable nano-sized microemulsions were identified and formulated into phenytoin loaded hydrogels. The physicochemical properties of the formulations were evaluated in term of emulsion stability index, droplet size, zeta potential, pH, and rheological properties. The efficacy of in vitro drug release of phenytoin was further evaluated using Franz diffusion cells.Results: Stability study revealed that ten lipid emulsions mixing with surfactant Tween 80 at an oil-to-surfactant ratio of 1:9 having 100% emulsion stability indices. Among these, two emulsions (F6 and F21) were identified as the most stable nano-sized microemulsions with clear and transparent appearances; mean droplet size maintained within 100 nm (11–16 nm) as per stability study. Rheological data showed that all phenytoin is loaded hydrogels exhibited non-Newtonian and shear-thinning flow behavior, with high yield stress of a 10.3–18.8 Pa. The in vitro release profiles followed the first-order kinetic model, with R2&gt;0.95, where F21 demonstrated the highest release rate, with 93.12% drug released in 12 h.Conclusion: These findings concluded that CKO/SBO blend microemulsion hydrogel has the highest potential for topical phenytoin delivery.

Phenytoin induces in vitro melanocyte proliferation

Phenytoin (5,5 diphenylhydantoin), a widely-used anticonvulsant, has been employed both topically and systemically in the treatment of some dermatological disorders. Immunological and non-immunological defects suggests that phenytoin could be therapeutically effective for vitiligo repigmentation. The first objective was to evaluate the effect of phenytoin on cultures of normal human melanocytes and to assess cytotoxicity of the substance using colorimetric methods. The second objective was to select the topical product that releases phenytoin best and fastest, for further clinical studies in vitiligo patients. In the first part of the study, we exposed normal human epidermal melanocyte cultures at 5,5 diphenylhydantoin at different concentrations. Melanocyte proliferation was evaluated using colorimetric assays (MTS assay), by measuring the absorbance at 490 nm with an ELISA plate reader. In the second part of the study, we formulated and obtained three types of phenytoin topical preparations: gel, hydrophilic cream, and ointment, for evaluation of the in vitro phenytoin release. Results The statistical analysis revealed that at low concentrations (0.1, 0.5 μg/ml), phenytoin stimulates growth and cellular proliferation in melanocyte cultures. The in vitro study of drug release indicated that gel formulation gives the highest phenytoin release. Our result indicates that topical applications of low concentrations of phenytoin may have beneficial effects in vitiligo, which justifies its further testing on clinical trials. Our gel formulation occurred to be the most suitable for the clinical studies.

Influence of Water/Alkoxide Ratio in the Synthesis of Nanosized Sol−Gel Titania on the Release of Phenytoin

The sol-gel method was used to synthesize inorganic reservoirs with encapsulated antiepileptic drug phenytoin. The drug release profile was shown to depend on the morphology and surface properties of the matrix. A parameter of the synthesis such as water/alkoxide ratio r(w) was varied in order to investigate its influence on the matrix properties and as a result on the drug release profile. It was found that the specific surface area and crystallization degree decrease with an increase of r(w), whereas the hydroxyl group coverage increases with an increase of r(w). Drug release kinetics studies revealed that the initial release rate increases with an increase of water content in the reaction, whereas the long time release rate first slightly increases with an increase of water content from 4 to 8 and then decreases for r(w) = 16. The interplay of different parameters of the matrix is shown to be responsible for such a dependence and is discussed in the Article.

Controlled release of phenytoin for epilepsy treatment from titania and silica based materials

Template technique was used to obtain well ordered nanostructured materials: mesoporous silica and nanostructured titania tubes. This technique permits the synthesis of solids with controlled mesoporosity, where a large variety of molecules that have therapeutic activity can be hosted and further released to specific sites. In this work phenytoin (PH), a drug used in epilepsy treatment, was loaded in ordered mesoporous silica (SBA 15) and nanostructured titania tubes (TiO 2). The pure materials and those containing PH were characterized by X-ray diffraction, FTIR spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and N 2 adsorption–desorption at 77 K. In order to determine the loading capacity of the antiepileptic drug on these silica- and titania-based materials, the loading and release of PH was investigated using UV–vis spectroscopy. Tubular structures were found for the titania samples, for which the X-ray diffractograms showed to be formed by anatase and rutile phases. On the other hand, an amorphous phase was found in the silica sample. A highly ordered hexagonal structure of 1D cylindrical channels was also observed for this material. Loaded PH showed a good stability inside the used materials as observed by spectroscopy analysis. The adsorption and desorption of PH are faster in nanostructured TiO 2 tubes than in mesoporous silica matrix.

Study of Formulation Factors Influencing Phenytoin Release Rate from Alginate–Chitosan Microparticles using an Experimental Design Approach

first_page settings Order Article Reprints Font Type: Arial Georgia Verdana Font Size: Aa Aa Aa Line Spacing:    Column Width:    Background: Open AccessConference Report Study of Formulation Factors Influencing Phenytoin Release Rate from Alginate–Chitosan Microparticles using an Experimental Design Approach by N. CEKIĆ 1,*, B. ČALIJA 2, S. SAVIĆ 2 and J. MILIĆ 2 1 DCP Hemigal, Leskovac, Serbia 2 Faculty of Pharmacy, Belgrade University, Belgrade, Serbia * Author to whom correspondence should be addressed. Sci. Pharm. 2010, 78(3), 602; https://doi.org/10.3797/scipharm.cespt.8.PDD13 Received: 12 July 2010 / Accepted: 12 July 2010 / Published: 12 July 2010 Download Download PDF Versions Notes Abstract Alginate-based microparticles have been widely investigated for applications like enzyme immobilization, immunoisolation in cell transplantation and drug release systems. [...] Share and Cite MDPI and ACS Style CEKIĆ, N.; ČALIJA, B.; SAVIĆ, S.; MILIĆ, J. Study of Formulation Factors Influencing Phenytoin Release Rate from Alginate–Chitosan Microparticles using an Experimental Design Approach. Sci. Pharm. 2010, 78, 602. https://doi.org/10.3797/scipharm.cespt.8.PDD13 AMA Style CEKIĆ N, ČALIJA B, SAVIĆ S, MILIĆ J. Study of Formulation Factors Influencing Phenytoin Release Rate from Alginate–Chitosan Microparticles using an Experimental Design Approach. Scientia Pharmaceutica. 2010; 78(3):602. https://doi.org/10.3797/scipharm.cespt.8.PDD13 Chicago/Turabian Style CEKIĆ, N., B. ČALIJA, S. SAVIĆ, and J. MILIĆ. 2010. "Study of Formulation Factors Influencing Phenytoin Release Rate from Alginate–Chitosan Microparticles using an Experimental Design Approach" Scientia Pharmaceutica 78, no. 3: 602. https://doi.org/10.3797/scipharm.cespt.8.PDD13 Find Other Styles Article Metrics No No Article Access Statistics For more information on the journal statistics, click here. Multiple requests from the same IP address are counted as one view.

Controlled Release of Phenytoin from Nanostructured TiO&lt;SUB&gt;2&lt;/SUB&gt; Reservoirs

Controlled Release of Phenytoin from Nanostructured TiO&lt;SUB&gt;2&lt;/SUB&gt; Reservoirs

Formulation and in vitro and in vivo characterization of a phenytoin self-emulsifying drug delivery system (SEDDS)

The aim of this study is to develop and characterize a self-emulsifying drug delivery system (SEDDS) of phenytoin, and to compare its relative bioavailability to a commercially available suspension. Four phenytoin SEDDS were prepared and evaluated. Following emulsification, the optimized formula was selected to have the smallest mean particle size and the highest absolute zeta potential, which should yield the formation of a stable emulsion. Its dissolution characteristics were superior to the other SEDDS formulas. In vivo and in vitro tests were run to compare the optimized formula, SEDDS II, to a commercially available Dilantin ® suspension. The in vitro dissolution indicated a significant improvement in phenytoin release characteristics. The in vivo study using male rats showed a clear enhancement in phenytoin oral absorption from SEDDS compared to Dilantin ® suspension. The area under the curve AUC (−10 min→10 h) of phenytoin after SEDDS administration increased by 2.3 times compared to Dilantin ® ( p < 0.05), and the rate of absorption of phenytoin was significantly faster from the SEDDS. The concentration after 30 min ( C 30 min ) of SEDDS administration was 4.9 times higher than C 30 min after Dilantin ® administration ( p < 0.05). A sustained effect of phenytoin in plasma was also observed. After 12 weeks storage, SEDDS II was found to be chemically and physically stable under stressed conditions.

Sustained release of phenytoin following the oral administration of phenytoin sodium/ethylcellulose microcapsules in human subjects and rabbits.

Phenytoin sodium was microencapsulated with ethylcellulose (EC) by a coacervation-phase separation method from ethyl acetate solution to develop a prolonged release dosage form of phenytoin. Release of phenytoin from the microcapsules (phenytoin sodium/EC) was evaluated by the JP dissolution test in JP disintegration media No. 1 and No. 2. The release rates of phenytoin from phenytoin sodium powders were extremely rapid in both media, however, the release rates from the microcapsules were much more retarded. Following the oral administration of microcapsules to rabbits, prolonged plasma concentrations of phenytoin were obtained, while microcapsules orally administered to human subjects showed prolonged urinary excretion of phenytoin metabolites.

Preparation of chitosan-reinforced alginate gel beads — effects of chitosan on gel matrix erosion

Chitosan-reinforced alginate gel beads were prepared and the release patterns of coloring matter (Brilliant Blue G, BB) held within them were investigated. The release rates of BB from the gel beads were much slower after an initial lag time when they were incubated with chitosan compared with the original intact gels prepared without chitosan. These differences were observed irrespective of the β- d-mannuronic acid/α- l-guluronic acid (M/G) ratio of the alginate used and an additive effect on the release rate was observed when two species of alginates were combined. The initial release rates were reduced gradually in proportion to the increases in the chitosan concentration and/or incubation times used when preparing the gel beads. Furthermore, erosion of the gel beads was suppressed by chitosan treatment. The release of phenytoin from alginate gel beads showed the same characteristics as that of BB.

Pancreatic lipase-catalyzed hydrolysis of esters of hydroxymethyl phenytoin dissolved in various metabolizable vehicles, dispersed in micellar systems, and in aqueous suspensions.

Lipase-catalyzed hydrolysis of fatty acid esters of 3-hydroxymethyl phenytoin was studied in various triglyceride and ethyl oleate emulsions, dispersed in micellar solutions, and suspended in an aqueous buffered solution. Phenytoin release from ethyl oleate emulsions of the prodrugs show apparent first-order kinetics with the pentanoate to nonanoate derivatives and sigmoidal kinetics with the long-chain fatty acid derivatives (stearate and oleate). A transition in the kinetic behavior, between the short- and the long-chain acyl prodrugs, was observed with the decanoate derivative. These observations are accounted for by a proposed kinetic model. Phenytoin release from the solid prodrugs follows zero-order kinetics and is independent of the total amounts of suspended material but directly proportional to the lipase concentration. Lipolysis of the solid suspended prodrugs was dependent on the length of the acyl side chain of the prodrug, with maxima for the pentanoate and the octanoate derivatives. The short-chain derivatives, acetate and propionate, as well as the long-chain prodrug, stearate, showed the slowest lipolysis rate when present as solid dispersions. The zero-order rate is qualitatively correlated with the melting point of the prodrugs. This result might be expected if the melting point is taken as a measure of the cohesivity or packing of the molecules at the surface of a crystal.

Phenytoin Prodrugs VI: In Vivo Evaluation of a Phosphate Ester Prodrug of Phenytoin after Parenteral Administration to Rats

Tissue damage caused by subcutaneous and intramuscular administration of three phenytoin prodrugs to rats was assessed. Since two of the prodrugs caused significant irritation, only 3-(hydroxymethyl)-5,5-di-phenylhydantoin disodium phosphate ester might be useful as a nonirritant phenytoin prodrug suitable for parenteral administration. To confirm the release of phenytoin from this prodrug, phenytoin availability after intramuscular and intravenous administrations of the phosphate prodrug was evaluated in rats and compared with sodium phenytoin. The prodrug quantitatively released phenytoin after intravenous administration, and phenytoin levels from intramuscular administration of the prodrug were far superior to those generated from similarly administered sodium phenytoin. Based on this and earlier studies, it was concluded that this prodrug should be further assessed as a parenteral form of phenytoin.

Some factors influencing the in vitro release of phenytoin from formulations

Usinga stirred flask method the dissolution behaviour of formulations containing sodium phenytoin or phenytoin acid have been compared. In general the release pattern from capsules is more complex than that from tablets. The pH of the dissolution medium requires to be specified with accuracy. Formulation variables which affect release are particle size, packing of the capsule and the nature of the diluent. The formation of ' insoluble calcium or magnesium salts from formulation adjuvants is believed to occur and may be a factor which should receive further attention both in vitro and in vivo.