Pharmacokinetic,Tissue Distribution,and Excretion of Puerarin and Puerarin-Phospholipid Complex in Rats

ABSTRACT

Puerarin is a potential therapeutic agent for cardiovascular diseases. But its poor oral bioavailability restricts its clinical application. In present study, as an evaluation of a formulation to improve the bioavailability of the drug, puerarin and its phospholipid complex were given to rats by intragastrically (i.g.) administration to compare pharmacokinetic, tissue distribution, and excretion. Serum samples were obtained at designated times after a single oral dose of 400 mg/kg puerarin or its complex. Tissue samples (heart, liver, spleen, kidney, lung, and brain), urine, and feces were collected and analyzed by a sensitive and specific high performance liquid chromatography (HPLC) method after i.g. administration of puerarin or its phospholipid complex. Compartmental and non-compartmental analyses were applied to the serum concentration versus time data. Pharmacokinetic parameters were calculated using the 3P97 pharmacokinetic software package. An open two-compartment, first-order model was selected for pharmacokinetic modeling. The results showed that after i.g. administration of 400 mg/kg puerarin and its phospholipid complex (equivalent to 400 mg/kg of puerarin), the pharmacokinetic parameters of the two formulations were different. The serum concentrations reached peaks at 0.894 ± 0.521 h and 0.435 ± 0.261 h, respectively, indicating the complex was more readily absorbed in serum than puerarin. The maximum concentrations for puerarin and its complex were 1.367 ± 0.586 mg·L^?1 and 2.202 ± 1.28 mg·L^?1 and AUC were 5.779 ± 1.662 mg·h. L^?1 and 8.456 ± 0.44 mg·h L^?1, respectively, indicating a higher bioavailability for the complex. The widely distribution characteristics of puerarin and its complex in tissues post-i.g. administration was identical and in a descending order as follows: lung, kidney, liver, heart, spleen, and brain. However, the amount was different. Puerarin distribution was higher in heart, lung, and brain after administering the complex. The cumulative 72 h urinary excretion of puerarin after i.g. administration of puerarin and its complex accounted for 1.05%, 1.11% of the administered dose, respectively. The cumulative feces excretion of puerarin was 32.3% and 25.5%. To sum up, oral administration of puerarin phospholipid complex modified the pharmacokinetics and tissue distribution of puerarin and it could be an effective oral formulation for puerarin.     

A microemulsion of puerarin–phospholipid complex for improving bioavailability: preparation,in vitro and in vivo evaluations

Puerarin is a phytochemical with various pharmacological effects, but poor water solubility and low oral bioavailability limited usage of puerarin. The purpose of this study was to develop a new microemulsion (ME) based on phospholipid complex technique to improve the oral bioavailability of puerarin. Puerarin phospholipid complex (PPC) was prepared by a solvent evaporation method and was characterized by X-ray diffraction and infrared spectroscopy. Pseudo-ternary phase diagrams were constructed to investigate the effects of different oil on the emulsifying performance of the blank ME. Intestinal mucosal injury test was conducted to evaluate safety of PPC-ME, and no sign of damage on duodenum, jejunum and ileum of rats was observed using hematoxylin-eosin staining. In pharmacokinetic study of PPC-ME, a significantly greater C_max (1.33?µg/mL) was observed when compared to puerarin (C_max 0.55?µg/mL) or PPC (C_max 0.70?µg/mL); the relative oral bioavailability of PPC-ME was 3.16-fold higher than puerarin. In conclusion, the ME combined with the phospholipid complex technique was a promising strategy to enhance the oral bioavailability of puerarin.     

Enhanced Oral Bioavailability of Puerarin Using Microemulsion Vehicle

The main purpose of this study was to prepare puerarin microemulsion system to improve oral bioavailability of puerarin. The microemulsion formulations were prepared using soybean oil, soybean lecithin/ethyl lactate (1:1), and 1,2-propanediol/water. The presence of microemulsion regions were investigated by pseudo-ternary phase diagrams. The droplet size of microemulsion was characterized by photo-correlation spectroscopy. In vivo pharmacokinetic study was conducted in mice, and the results indicated that AUC_0→∞ was 15.82-fold higher than that of puerarin suspension upon oral administration. Particles of puerarin microemulsion were round and homogeneous. Puerarin microemulsion also showed good stability. These studies showed that microemulsion system of puerarin might be promising vehicles for the peroral delivery of puerarin.     

Relative Bioavailability and Pharmacokinetic Parameters Following Adminstration of Single Oral Dose (2×150 mg) of Chloroquine Tablet in Healthy Subjects

The bioavailability ot Chloroquine phosphate (150 mg base) film coated tablet (manufactured by Pars - Darou Co. Iran) was compared with that ot the Resochin tablet (Bayer, Germany) in seven healthy male and female volunteers. Blood samples were collected up to 14 days utter oral dosing of 300 nig and chloroquine serum concentrations were determined by means ot High Performance Liquid Chromatography (HPLC). From the analysis ot serum samples the following pharmacokinetic parameters were obtained: the absorption rate of test tablet and that of reference were 0.25 h^-1 and 0.34 h^-1 respectively; maximum serum concentration of both tablets was nearly equal, 81.6±25 and 83.4±27 ng/ml (for test and reference tablets respectively); time to reaching C_max (t_max) was also very similar, 4±1.6 for test and 4±1.0 h for reference; the area under the serum concentration-time curve [AUC(O -)] of 6976 ng.ml^-1.h±1967 for test and 6446 ng.ml^-1.h ± 2460 for reference tablets were found using trapezoidal rule. By evaluating of the r=(T/R)×100 for each parameters, the test tablet was found to be bioequivalent to Resochin at p = 0.05.     

Preparation,Characterization, and Bioavailability of Ursodeoxycholic Acid–Phospholipid Complex In Vivo

The aim of this study was to prepare ursodeoxycholic acid–phospholipid complex (UDCA-PLC) to enhance oral bioavailability of UDCA, and the physicochemical properties of the complex were studied. Compared with those of UDCA tablet after oral administration in rats, the main pharmacokinetic characteristics and bioavailability of UDCA-PLC orally administered were evaluated. Tetrahydrofuran was used as a reaction medium, UDCA and phospholipids were resolved into the medium, and UDCA-PLC was formed after the organic solvent was evaporated off under vacuum condition. The physicochemical properties of the complex were evaluated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction, particle size distribution analysis, and n-octanol/water partition coefficient (P) study. The blood concentrations of UDCA-PLC and UDCA tablet at different time points after oral administration in rats were assayed by high-performance liquid chromatography (HPLC) after derivatization. The pharmacokinetic parameters were computed by software program 3p87. The X-ray diffraction and DSC studies showed that UDCA and phospholipids in the UDCA-PLC were combined by noncovalent bond, not forming a new compound, and n-octanol/water partition coefficient (P) of UDCA-PLC was effectively enhanced. The mean serum concentration–time curves of UDCA after oral administration of UDCA-PLC and UDCA tablet in rats were both in accordance with open two-compartment model. Pharmacokinetic parameters of UDCA tablet and the PLC in rats were T_max 1.9144 and 1.5610 h, C_max 0.0576 and 0.1346 μg/mL, and AUC_0–∞ 4.736 and 11.437 μg h/mL, respectively. The bioavailability of UDCA in rats was significantly different (p < .05) compared with those of UDCA tablet after administration. The UDCA-PLC would be more prospective formulation in future.     

Preparation and pharmacokinetics in rabbits of breviscapine unilamellar vesicles

The purpose of the study was to prepare the unilamellar liposomal vesicles of breviscapine (Breviscapine-LUVs) and investigate the pharmacokinetics of Breviscapine-LUVs in rabbits. Breviscapine-LUVs were prepared by the film dispersion method and treated further by extrusion. Its size distribution and zeta potential were determined by photon correlation spectroscopy. The encapsulation efficiency (EE) and cumulative release of Breviscapine-LUVs were assayed by the dialysis method. The crossover design (two periods) was used in six rabbits, which were administered Breviscapine-LUVs and reference preparation. Results showed that the particle size of Breviscapine-LUVs was 50.8 nm, and the polydispersity index was 0.287. The zata potential was -24 mV ± 9 mV(n = 3), and the EE% was 81.1 ± 1.1% (n = 3). The cumulative release of vesicles in 0.9% NaCl was 17.2 ± 0.78%, 26.1 ± 0.68%, and 29.9 ± 0.81% in 2, 8, and 24 h, respectively. The mean concentration-time curves of breviscapine liposomes and reference preparation were both fitted to a two-compartment model with the main pharmacokinetic parameters as follows: t_1/2β of Breviscapine-LUVs and reference preparation were (42.5 ± 28.6) min and (6.01 ± 4.64) min, respectively; CL_(s) were (15.3 ± 9.03) mL × min^-1 and (84.6 ± 40.6) mL × min^-1, respectively; AUC_0-300 were (1267 ± 1083) μg × min × mL^-1 and (196 ± 107) μg × min × mL^-1, respectively. Compared with the reference preparation, breviscapine liposomes had a much higher concentration in plasma and contained characteristic of sustained-release, which ameliorated the pharmacokinetic properties of scutellarin.     

In vitro studies on transdermal permeation of butorphanol

The influence of the donor vehicles pH and the addition of laurocapram or transkarbam 12 as permeation enhancers on the transdermal permeation of butorphanol through human skin were examined with the aim of finding out about its possible use in the transdermal delivery system. As the pH of the donor vehicles rises, the mean value of butorphanol skin fluxes declines; an exponential relationship of the means of butorphanol flux values against the pH of the buffered aqueous donor vehicles has been demonstrated. The presence of 1% of transkarbam 12 (T12) or 5% of laurocapram (LC), respectively, in an isopropylmyristate (IPM) donor vehicle increased transdermal fluxes of butorphanol almost 2.5 times (58.1 ± 5.7 μg cm^-2 hr^-1) or 1.5 times (36.4 ± 7.0 μg cm^-2 hr^-1), respectively, when compared to blank donors. Considering clinical and pharmacokinetic data on butorphanol, it is possible to expect that a transdermal preparation sized 20 cm² and possessing flux values ranging between 5.1 and 15.3 μg cm^-2 hr^-1 should be sufficient to achieve effective butorphanol transdermal fluxes, namely using IPM donors containing T12. In conclusion, butorphanol is a suitable candidate for transdermal administration and T12 is a very a suitable enhancer for it.     

Self-Microemulsifying Drug Delivery Systems (SMEDDS) for Improving In Vitro Dissolution and Oral Absorption of Pueraria Lobata Isoflavone

The aim of our investigation was to develop and characterize self-microemulsifying drug delivery systems (SMEDDS) of Pueraria lobata isoflavone to improve its in vitro dissolution and oral absorption in beagle dogs. SMEDDS consisted of oil (ethyl oleate), a surfactant (Tween 80), and a cosurfactant (Transcutol P). In all the SMEDDS, the level of Pueraria lobata isoflavone was fixed at 20% w/w of the vehicle. The in vitro self-microemulsification properties and droplet size analysis of SMEDDS were studied following their addition to water under mild agitation. A pseudoternary phase diagram was constructed identifying the efficient self-microemulsification region. From these investigations, an optimized formulation was selected and its dissolution and bioavailability were compared with a tablet formulation in beagle dogs. The in vitro dissolution rate of puerarin from SMEDDS was more than threefold faster than that from Yufengningxin tablets (Pueraria lobata isoflavone tablets). A 2.5-fold increase in the relative bioavailability was observed for the SMEDDS compared with Yufengningxin tablets. The absolute bioavailability of the SMEDDS was 82.32 ± 15.51%, which was significantly improved compared with that of Yufengningxin tablets. These results demonstrate the potential of SMEDDS as an efficient way of improving the oral absorption of Pueraria lobata isoflavone.     

Investigation of nanostructured lipid carriers for transdermal delivery of flurbiprofen

The aim of this study was to develop nanostructured lipid carriers (NLC) for transdermal delivery of Flurbiprofen (FP). The physical stability of FP-NLC and its in vitro permeation profile were investigated. After three months of storage at 4°C, 20°C, and 40°C, no significant differences between the evaluated parameters, such as pH value, the entrapment efficiency, particle size, and zeta potential were observed. In in vitro permeation studies, the cumulative permeated amounts and the release rate from FP-NLC were 412.53 ± 21.37 μg/cm² and 35.25 μg/cm²/h after 12 h (n = 6), respectively, while from saturated FP-PBS (pH = 7.4) were 90.83 ± 8.67 μg/cm² and 6.99 μg/cm²/h, respectively. These results indicated that the FP-NLC were with good physical stability and were able to improve the permeated amounts and the release rate of FP. It could potentially be exploited as a carrier with improved drug entrapment efficiency and permeated amount in the transdermal delivery of FP.     

Preparation, characterization, and bioavailability of ursodeoxycholic acid-phospholipid complex in vivo

The aim of this study was to prepare ursodeoxycholic acid-phospholipid complex (UDCA-PLC) to enhance oral bioavailability of UDCA, and the physicochemical properties of the complex were studied. Compared with those of UDCA tablet after oral administration in rats, the main pharmacokinetic characteristics and bioavailability of UDCA-PLC orally administered were evaluated. Tetrahydrofuran was used as a reaction medium, UDCA and phospholipids were resolved into the medium, and UDCA-PLC was formed after the organic solvent was evaporated off under vacuum condition. The physicochemical properties of the complex were evaluated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction, particle size distribution analysis, and n-octanol/water partition coefficient (P) study. The blood concentrations of UDCA-PLC and UDCA tablet at different time points after oral administration in rats were assayed by high-performance liquid chromatography (HPLC) after derivatization. The pharmacokinetic parameters were computed by software program 3p87. The X-ray diffraction and DSC studies showed that UDCA and phospholipids in the UDCA-PLC were combined by noncovalent bond, not forming a new compound, and n-octanol/water partition coefficient (P) of UDCA-PLC was effectively enhanced. The mean serum concentration-time curves of UDCA after oral administration of UDCA-PLC and UDCA tablet in rats were both in accordance with open two-compartment model. Pharmacokinetic parameters of UDCA tablet and the PLC in rats were T(max) 1.9144 and 1.5610 h, C(max) 0.0576 and 0.1346 microg/mL, and AUC(0-infinity) 4.736 and 11.437 microg h/mL, respectively. The bioavailability of UDCA in rats was significantly different (p < .05) compared with those of UDCA tablet after administration. The UDCA-PLC would be more prospective formulation in future.     

The use of lipid-based formulations to increase the oral bioavailability of Panax notoginseng saponins following a single oral gavage to rats

Purpose: This article was intended to improve the absorption of ginsenoside Rg1 and Rb1 of Panax notoginseng saponins (PNS). Methods: PNS-Phospholipid complex and a lipid-based formulation by dissolving the complex in the medium chain fattyglycerides were prepared, and their oral relative bioavailability was determined in rats and compared with an aqueous solution of PNS for each component. Results: The study gave evidence that the phospholipids could combine with the two active constitutes of PNS and form a PNS-phospholipid complex. The complex efficiently increased the solubility of hydrophilic ginsenoside Rg1 and Rb1 in some selected hydrophobic esters, such as fatty glycerides, and constructed the lipid-based formulations of PNS. The experimental result in rats in vivo showed that the oral relative bioavailability was enhanced remarkably by these lipid-based formulations composed of the PNS-Phospholipid complex and various esters. The absorption enhancement of the medium-chain glyceride (Labrafac cc and Capmul MCM (3:1)) was somewhat greater than that of other fatty glyceride. The area under the plasma concentration-time curve (AUC) of ginsenoside Rg1 and Rb1 of the PNS-complex in the medium-chain glyceride were 27.38 μg.mL-1.h and 600.08 μg.mL-1.h, compared with 2.52 μg.mL-1.h and 92.29 μg.mL-1.h of the PNS aqueous solution, respectively. Conclusions: The oral relative bioavailability of ginsenoside Rg1 and Rb1 of PNS was enhanced remarkably by the lipid-based formulations. These findings reveal a new strategy to increase oral bioavailability by lipophilicity enhancement for some highly water-soluble but poorly absorbed drugs.     

A combination of complexation and self-nanoemulsifying drug delivery system for enhancing oral bioavailability and anticancer efficacy of curcumin

Abstract

Objective: Curcumin, the golden spice from Indian saffron, has shown chemoprotective action against many types of cancer including breast cancer. However, poor oral bioavailability is the major hurdle in its clinical application. In the recent years, self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising tool to improve the oral absorption and enhancing the bioavailability of poorly water-soluble drugs. In this context, complexation with lipid carriers like phospholipid has also shown the tremendous potential to improve the solubility and therapeutic efficacy of certain drugs with poor oral bioavailability.

Methods: In the present investigation, a systematic combination of both the approaches is utilized to prepare the phospholipid complex of curcumin and facilitate its incorporation into SNEDDS. The combined use of both the approaches has been explored for the first time to enhance the oral bioavailability and in turn increase the anticancer activity of curcumin.

Results: As evident from the pharmacokinetic studies and in situ single pass intestinal perfusion studies in Sprague–Dawley rats, the optimized SNEDDS of curcumin–phospholipid complex has shown enhanced oral absorption and bioavailability of curcumin. The cytotoxicity study in metastatic breast carcinoma cell line has shown the enhancement of cytotoxic action by 38.7%. The primary tumor growth reduction by 58.9% as compared with the control group in 4T1 tumor-bearing BALB/c mice further supported the theory of enhancement of anticancer activity of curcumin in SNEDDS.

Conclusion: The developed formulation can be a potential and safe carrier for the oral delivery of curcumin.     

非晶Nd-Ni-B/NF稀土复合电极材料的制备及其析氢性能

本研究采用简单的一步化学沉积法制备非晶纳米Nd-Ni-B/NF稀土复合电极并研究其析氢(Hydrogen evolution reaction, HER)性能。通过各种测试方法对纳米电极材料进行物相分析和形貌表征,并探索其电催化析氢性能和稳定性。结果表明, 稀土Nd可提高电极的电催化析氢性能, 当硝酸钕浓度为3 g?L^-1时, 恒温35 ℃下施镀1 h, 制备的Nd-Ni-B/NF电极析氢性能最佳。Nd-Ni-B/NF(Nickel foam)电极在1.0 mol?L^-1KOH 溶液中, 20 mA?cm^-2电流密度下的析氢过电位仅为180 mV, Tafel斜率为117 mV?dec^-1, 析氢反应由Volmer-Heyrovsky步骤控制。此外, Nd-Ni-B/NF电极具有优越的电化学稳定性, 在持续电解12 h或2000次循环伏安测试后, 催化剂的活性没有明显衰减。     

Piroxicam benzoate--synthesis,HPLC determination,and hydrolysis

An improved method of piroxicam benzoate synthesis was described, and an isocratic reversed-phase high-performance liquid chromatography method for its determination was developed and fully validated. The method was found to be specific, precise (relative standard deviation 0.3%), accurate (mean recovery 99.9%), and robust. Limit of detection was estimated at 0.055 µg mL^-1 and limit of quantification at 0.185 µg mL^-1. The kinetics of piroxicam benzoate hydrolysis in aqueous buffer solutions (pH 1.1 and 10), simulated gastric and intestinal fluids was studied. The hydrolysis followed first-order kinetics. The following rate constants were obtained at pH 10: k = 1.8 × 10^-3 hr^-1 at 37°C and k = 3.4 × 10^-2 hr^-1 at 60°C. In acidic media, no significant hydrolysis was observed after 24 hr. During the 24-hr period in simulated intestinal fluid, only 10.9% of the starting ester was hydrolyzed.     

A torsion–effusion study on the sublimation of Cu2Te

The sublimation of Cu₂Te was studied and its vapor pressure was measured by the torsion method. In the covered temperature range, the temperature dependence of the total vapor pressure can be expressed by the following equation: log p (kPa)=(6.17±0.20)−(11 680±300)(K/T) (1084–1234 K). The sublimation process of Cu₂Te is incongruent, and Te(g) and Te₂(g) being the only gaseous species present in the vapor, the partial sublimation reactions were studied: Cu₂Te(s)→2Cu(s)+Te(g), 2Cu₂Te(s)→4Cu(s)+Te₂(g). The standard sublimation enthalpies of these reactions, Δ_rH⁰(298)=254±10 and 248±8 kJ, respectively, were derived by the second- and third-law treatment of the pressure data. The heat of formation of Cu₂Te, Δ_fH⁰(298)=−43±6 kJmol⁻¹, was also derived.     

Effects of adsorbent dose, its particle size and initial arsenic concentration on the removal of arsenic, iron and manganese from simulated ground water by Fe3+ impregnated activated carbon

This paper presents the observations of the study on arsenic removal from a contaminated ground water (simulated) by adsorption onto Fe³⁺ impregnated granular activated carbon (GAC-Fe). Fe²⁺, Fe³⁺ and Mn²⁺ have also been considered along with arsenic species in the water sample. Similar study has also been done with untreated granular activated carbon (GAC) for comparison. The effects of adsorbent dose, particle size of adsorbent and initial arsenic concentration on the removal of As(T), As(III), As(V), Fe²⁺, Fe³⁺ and Mn²⁺ have been discussed. Under the experimental conditions, the optimum adsorbent doses for GAC-Fe and GAC have been found to be 8 g/l and 24 g/l, respectively with an agitation time of 15 h. Particle size of the adsorbents (both GAC and GAC-Fe) has shown negligible effect on the removal of arsenic and Fe species. However, for Mn removal the effect of adsorbent particle size is comparatively more. Percentage removal of As(T), As(V) and As(III) increase with the decrease in initial arsenic concentration (As₀). However, the increase in percentage removal of all the arsenic species with decrease in As₀ are less for higher value of As₀ (3000–500 ppb) than those of the lower value of As₀ (500–10 ppb). The % removal of As(T), As(III), As(V), Fe, and Mn were 95%, 92.4%, 97.6%, 99% and 41.2%, respectively when 8 g/l GAC-Fe was used at the As₀ value of 200 ppb. However, for GAC these values were 55.5%, 44%, 71%, 98% and 97%. The pH and temperature of the study were 7 ± 0.1 and 30 ± 1 °C, respectively.     

Inclusion Complexes of Tolnaftate with β-Cyclodextrin and Hydroxypropyl β-Cyclodextrin

Tolnaftate, an antifungal agent, was found to form inclusion complexes with both β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrins (HPBCDs) with two different degrees of substitution [HPBCD(A)-8% and HPBCD(B)-3%]. Complex formation in the solution state was studied using phase solubility and spectral shift methods. Solid complexes were prepared by the coprecipitation method. Solubilities and dissolution rates were determined for each solid complex, its corresponding physical mixture, and free drug. The increase in solubility of tolnaftate with added HPBCD was found to be significantly greater than with added β-CD. For both HPBCD(A) and HPBCD(B), over the concentration range 0-0.05 M. 1:1 complexes with stability constants of 1460 ± 139 M^-1 and 1860 ± 165 M^-1 were observed, respectively. Over the β-CD concentration range 0-0.02 M, a 1:1 complex with a stability constant of 1190 ± 105 M^-1 was observed. At higher HPBCD concentrations, the increase in solubility was observed to show a positive deviation from linearity (type A_p phase diagram). Using the spectral method, in a 2 5% v/v methanol in water system, the stability constants were determined to be 1020 ± 150 M^-1 1110 ± 120 M^-1 and 1100 ± 260 M^-1 for HPBCD(A), HPBCD(B) and β-CD, respectively. The solid complexes prepared showed improved dissolution over physical mixtures and free drug.     

Average bioequivalence of clarithromycin immediate released tablet formulations in healthy male volunteers

The objective of this study was to assess average bioequivalence of two immediate released tablet formulations of 500-mg clarithromycin tablets in 24 healthy Thai male volunteers. In a randomized, single dose, fasting state, two-period, crossover study design with a 1-week washout period, each subject received a 500-mg clarithromycin tablet. Plasma samples were collected over a 24-hour period after oral administration and were analyzed by using a validated method using high performance liquid chromatography with electrochemical detection. Pharmacokinetic parameters were determined by using noncompartmental analysis. The time to reach the maximal concentration (t_max, h), the peak concentration (C_max, ng/mL), and the area under the curve (AUC_{0 - ∞}, ng.h/mL) of the Reference and Test formulations were 2.0 ± 0.8 vs. 2.2 ± 0.9, 2793 ± 1338 vs. 2642 ± 1344, and 17912 ± 7360 vs. 17660 ± 7992, respectively. Relative bioavailability was 0.99. The 90% confidence interval of C_max and AUC_{0 - ∞} were 82.6-112.1% and 84.7-112.0%. Bioequivalence between the Test and Reference formulation can be concluded.     

Evaluation of the physicochemical stability and skin permeation of glucosamine sulfate

Glucosamine sulfate (GS) is known to stop the degenerative process of osteoarthritis. Because most of the GS formulation on the market is in the oral form, an alternative formulation such as a transdermal delivery system (TDS) is necessary in order to increase patient compliance. As the initial step to develop a TDS of GS, the physicochemical stability and permeation study in rat skin were examined. Evaluation of the stability of GS at different pHs showed the compound to be most stable at pH 5.0. The degradation rate constant at 25°C was estimated to be 5.93 ×10^- 6 hr^- 1 (t₉₀~ 2.03 years) in a pH 5 buffer solution. Due to its hydrophilic characteristic, low skin permeability was expected of GS. However, the skin permeation rate was determined to be 13.27 µg/cm²/hr at 5% concentration. Results of this study suggest the possibility of developing GS into a transdermal delivery system.     

In vitro and in vivo evaluation of puerarin-loaded PEGylated mesoporous silica nanoparticles

Puerarin, which is extracted from Chinese medicine, is widely used in China and mainly used as a therapeutic agent for the treatment of cardiovascular diseases. Owing to its short elimination half-life in human beings, frequently intravenous administration of high doses of puerarin may be needed, which possibly leads to severe and acute side effects. The development of an effective sustained-release drug delivery system is urgently needed. In this study, PEGylated mesoporous silica nanoparticles (PEG-MSNs) had become a preferred way to prolong the half-life and improve the bioavailability of drugs. The release of puerarin from PEG-MSNs was pH dependent, and the release rate was much faster at lower pH than that at higher pH. Moreover, the PEG-MSNs exhibited improved blood compatibility over the MSNs in terms of low hemolysis, and it could also reduce the side effect of hemolysis induced by PUE. Compared with puerarin, PUE-loaded PEG-MSNs showed a 2.3-fold increase in half-life of puerarin and a 1.47-fold increase in bioavailability. Thus, the PEG-MSNs hold the substantial potential to be further developed as an effective sustained-release drug delivery system.