Preparation, Characterization and in Vitro Release of Ciprofloxacin Polylactic Acid Microspheres

Aim Ciprofloxacin polylactic acid microspheres (CFX-PLA-MS) were preparedusing solvent evaporation method from a solid-in-oil-in-water emulsion system. Methods Orthogonalexperiment was used to optimize the method of CFX-PLA-MS preparation. Microspheres werecharacterized in terms of morphology, size, encapsulation efficiency, drug loading and in vitro drugrelease. Results The physical state of CFX-PLA-MS was determined by scanning electron microscopy(SEM) and differential scanning calorimetry (DSC) . Microspheres formed were spherical with smoothsurfaces. Drug was enveloped in microspheres without mixing physically with PLA. The averageparticle size was 280.80 ± 0.15 μm, with over 90% of microspheres falling in the range of 250 -390 μm. The encapsulation efficiency was 65.8% ± 0.58% and the drug loading was 34.1% ± 0.51% .In vitro release study revealed a profile of sustained release of Ciprofloxacin from CFX-PLA-MS. Theaccumulated release percentage and half-life (T_(1/2) of Ciprofloxacin microspheres were 84.0% in53.2 h, and 31.9 h, respectively. Higuchi equation was Q= -0.0043 + 0.003 9 t^(1/2), r = 0.9941.Conclusion Ciprofloxacin microspheres have been successfully prepared and sustained release of CFXfrom microspheres is achieved.

Preparation and in vitro release studies of thymosin-loaded PLA microspheres

To obtain a kind of convenient oral dosage form of protein, which can be fully absorbed and is efficient and safe, the thymosin-loaded PLA（polylactic acid） microspheres are prepared by the emulsification- solvent evaporation method and the orthogonal design is used to optimize the technology of preparation. The form of the medicament microspheres of thymosin are proved by differential thermal analysis （DTA）. The drug content is determined by the Lowry method, and the package ratio of medicament microspheres of thymosin and drug release in vitro are calculated. The results show that the average diameter and encapsulation efficiency of the product prepared according to the optimized formulation are 13. 8 μm and 80. 7%, respectively. The in vitro release behavior within 12 h can be described by the Higuchi equation with T1/2 = 295 rain. There are no significant changes in size distribution and residual drug contents after being stored at 25℃ and 40 ℃ for 90 d, respectively. Due to the fact that its thymosin content and package ratio meet the requirement, and its releasing half life is long, the thymosin-loaded PLA microsohere has a favorable application future.

An accelerated method to evaluate thymopentin release from microspheres in vitro

To design an accelerated method to evaluate thymopentin release from PLGA microspheres in vitro. Microspheres were prepared by double emulsion technique, using poly（lactide-co-glycolide） （PLGA） as carrier. At higher medium temperature （45℃, 50℃ and 55℃）, an accelerated release testing in short time was studied and correlated with the conventional release （37℃） in vitro. The release in vitro of thymopentin from PLGA microspheres at 45 ℃, 50℃ and 55℃ was significantly accelerated （P 〈 0.05）. In particular, at 50℃, an accelerated release （30 h） of the hydrophilic peptide from the PLGA matrix was achieved and correlated well with the conventional release （30 d）. An accelerated release testing in vitro at higher temperature could be used to monitor thymopentin release from PLGA microspheres.

HPLC法测定TALICA缓释胶囊中3种主成分和葡甲胺的含量

目的基于高效液相色谱法(HPLC)建立TALICA缓释胶囊中阿莫西林、奥美拉唑镁、利福布汀3种主成分和葡甲胺辅料的含量.方法应用HPLC法,色谱柱为Agilent Zorbax SB-C18柱(150 mm×4.5 mm,5μm);流动相分别为乙腈(A)-磷酸盐缓冲液(B)和乙腈(A)-庚烷磺酸钠缓冲液(B),按时间程序梯度洗脱;VWD检测器,检测波长分别为254 nm和195 nm;进样量分别为10μL和20μL;流速均为1 mL·min^(-1);柱温分别为26℃和35℃;通过外标法计算阿莫西林、奥美拉唑镁、利福布汀3种主成分和葡甲胺辅料的含量.结果在波长254 nm下,阿莫西林、奥美拉唑镁、利福布汀分别在质量浓度0.02~2.12、0.02~2.16、0.02~2.16 mg·mL^(-1)内线性关系良好(r均大于0.9997),平均回收率分别为99.5%、98.9%、99.6%,RSD分别为0.5%、1.1%和0.6%,测得3种主成分的标示百分含量范围为98.8~101.1%.在波长195 nm下,葡甲胺在质量浓度1.00~50.00 mg·mL^(-1)内线性关系良好(r为0.9999),平均回收率及RSD为100.8%、0.9%,测得葡甲胺的平均含量为6.6%.结论HPLC法建立的TALICA缓释胶囊中阿莫西林、奥美拉唑镁、利福布汀3种主成分和葡甲胺辅料的含量测定分析方法稳定、简单、可靠,可用于TALICA缓释胶囊的质控研究.

Studies on in vitro release of cyclosporine A-loaded microspheres

Aim This study was to prepare cyclosporine A （CyA） microspheres （Ms） using 75：25 poly （D, L-lactide-co-glycolide） polymer （PLGA）, and to evaluate the in vitro release of the CyA microspheres. Methods CyA-Ms were prepared by an oil-inwater （o/w） emulsion solvent extraction/evaporation process and characterized for drug content, particle size, surface morphology, and differential scanning calorimeter （DSC）. Accelerated in vitro release of cyclosporine A from the mieropsheres was studied at various conditions, such as temperatures, surfactants, pH values and organic solvents for a short period. Results CyA-Ms were in spherical shape with average particle size of 50 μm and loading efficiency of 13.0%. The results of DSC measurements suggested that at the dry state, CyA did interact very strongly with the hydrophilic PLGA polymer. In vitro release test in various release medium showed slight increase of CyA-Ms release profiles under various conditions of temperatures, surfactants and pH values. However, dramatical increase of CyA-Ms release was seen in the medium containing 30% isopropanol. Conclusion It was demonstrated that CyA could be incorporated into polymeric Ms prepared from PLGA using a solvent evaporation technique. The release medium containing 30% isopropanol might be the ideal condition for CyA-PLGA microspheres in vitro quality control test.

Microstructure, Content and in vitro Release of Brucine and Strychnine in Strychnos Nux-Vomica Powder with Different Particle Sizes

To explore the effect of particle size on the quality uniformity and in vitro release performance of Strychnos nux-vomica powder, seven samples of Strychnos nux-vomica powder with different particle sizes were prepared.Microstructures and particle sizes were analyzed, and high performance liquid chromatography(HPLC) was used to test the contents and in vitro release performances of brucine and strychnine in the samples. Results showed that the contents and the in vitro release rates of brucine(or strychnine) in different samples were different since there are different proportions of endosperms to epidermal cells in Strychnos nux-vomica powder with different particle sizes. Brucine and strychnine in each sample were promptly released in the first ten minutes and their cumulative release rates were higher than 70% after ten minutes. Eighty minutes later, the cumulative release rate tended to be a constant. Considering the quality uniformity and safety of Strychnos nux-vomica powder used as traditional Chinese medicine, it would be better to control the particle size of Strychnos nux-vomica powder between 100 and 140 mesh in which the maximum cumulative release rate in vitro of brucine and strychnine can be relatively low within this range.

The effect of enzymes on release of trace elements in feedstuffs based on in vitro digestion model for monogastric livestock

Background: This experiment was conducted to study the effect of different feed enzymes(phytase,xylanase,β-glucanase) on release rate of trace elements(Fe,Cu,Mn and Zn) in 6 commonly used feedstuffs(corn,wheat,barley,soybean meal,wheat bran,wheat middlings) by using an in vitro model,simulating the digestive processes in stomach for 2 h and then in small intestine for 6 h at 39 °C.Results: Phytase raised(P < 0.05) the release rate of Cu and Zn in corn,Cu,Zn and Mn in wheat,Cu in barley,Cu,Zn and Mn in soybean meal,Zn,Fe in wheat bran and Zn,Fe,Mn in wheat middlings.The release rate of various trace elements in feedstuffs was increased after xylanase addition.Compared with the control group,the release rate of soluble Cu in corn,wheat,barley and soybean meal,soluble Zn in corn,wheat and wheat middlings and soluble of Mn in corn,wheat,barley and wheat bran increased(P < 0.05) after xylanase treatment.After the treatment of β-glucanase,the release rate of soluble Cu in corn,wheat and wheat bran,soluble Fe in barley,soybean meal and wheat bran and soluble Mn in corn and wheat bran all increased(P < 0.05) compared with the control group.In each feedstuff,after corresponding enzyme treatment,the contents of phytic acid,xylan and β-glucan were significantly lower than those of the control group(P < 0.05).Conclusions: Results showed that bound trace elements in feedstuffs can be released by feed enzymes.It may be necessary to take the trace elements in feedstuffs into account in the actual feed preparation including feed enzymes.

Release test of alliin/alliinase double-layer tablet by HPLC-Allicin determination

A simple, precise and accurate method was developed and validated for the determination of allicin release from alliin/alliinase double-layer tablets. According to Appendix XC Ⅱ of Chinese Pharmacopoeia 2010 edition Volume II, a small glass-method was adopted at the rotational speed of 100 r/min using 100 mL phosphate buffer （pH 6.8） as release medium. The release amount was determined by HPLC with a C18 column （250 mm × 4.6 mm, 5 μm） using the mobile phase consisting of methanol -0.4% carboxylic acid （65：35） at a flow rate of 1 mL/min and UV detection at 242 nm. The current method demonstrates good linearity over the range 4.052- 405.2 μg/mL （r2=0.9999） with an average recovery of 105.5%（RSD= 1.25%）. The accumulative release of alliin/alliinase double-layer tablets had good homogeneity for withinand betweenbatches. The method established is simple, accurate and repeatable for the determination of allicin release from alliin/alliinase double-layer tablets.

Sustained release donepezil loaded PLGA microspheres for injection:Preparation,in vitro and in vivo study

The purpose of this study was to develop a PLGA microspheres-based donepezil(DP)formulation which was expected to sustain release of DP for one week with high encapsulation efficiency(EE).DP derived from donepezil hydrochloride was encapsulated in PLGA microspheres by the O/W emulsion-solvent evaporation method.The optimized formulation which avoided the crushing of microspheres during the preparation process was characterized in terms of particle size,morphology,drug loading and EE,physical state of DP in the matrix and in vitro and in vivo release behavior.DP microspheres were prepared successfully with average diameter of 30m,drug loading of 15.92±0.31%and EE up to 78.79±2.56%.Scanning electron microscope image showed it has integrated spherical shape with no drug crystal and porous on its surface.Differential scanning calorimetry and X-ray diffraction results suggested DP was in amorphous state or molecularly dispersed in microspheres.The Tg of PLGA was increased with the addition of DP.The release profile in vitro was characterized with slow but continuous release that lasted for about one week and fitted well with first-order model,which suggested the diffusion governing release mechanism.After single-dose administration of DP microspheres via subcutaneous injection in rats,the plasma concentration of DP reached peak concentration at 0.50 d,and then declined gradually,but was still detectable at 15 d.A good correlation between in vitro and in vivo data was obtained.The results suggest the potential use of DP microspheres for treatment of Alzheimer’s disease over long periods.

Fabrication, characterization, in vitro drug release and glucose uptake activity of 14-deoxy,11, 12-didehydroandrographolide loaded polycaprolactone nanoparticles

Biodegradable polymer based novel drug delivery systems brought a considerable attention in enhancing the therapeutic efficacy and bioavailability of various drugs. 14-deoxy 11, 12-didehydro andrographolide(poorly water soluble compound) loaded polycaprolactone(nanoDDA) was synthesized using the solvent evaporation technique. Nano-DDA was characterized by scanning electron microscopy(SEM) and dynamic light scattering(DLS) studies. Fourier Transform InfraRed Spectroscopy(FTIR) was used to investigate the structural interaction between the drug and the polymer. Functional characterization of the formulation was determined using drug content, cellular uptake and in vitro drug release. 2-deoxy-D-[1-~3H] glucose uptake assay was carried out to assess the antidiabetic potential of nano-DDA in L6 myotubes.The nano-DDA displayed spherical shape with a smooth surface(252.898 nm diameter), zeta potential, encapsulation and loading efficiencies of -38.9 mV, 91.98 ± 0.13% and 15.09 ± 0.18% respectively. No structural alteration between the drug and the polymer was evidenced(FTIR analysis). Confocal microscopy studies with rhodamine 123 loaded polycaprolactone nanoparticles(Rh123-PCL NPs) revealed the internalization of Rh123-PCL NPs in a time dependent manner in L6 myoblasts. A dose dependent increase in glucose uptake was observed for nano-DDA with a maximal uptake of 108.54 ± 1.42% at 100 nM on L6 myotubes, thereby proving its anti-diabetic efficacy. A biphasic pattern of in vitro drug release demonstrated an initial burst release at 24 h followed by a sustained release for up to 11 days. To conclude,our results revealed that nano-DDA formulation can be a potent candidate for antidiabetic drug delivery.

Preparation and <i>in Vitro</i>Drug Release Evaluation of Once-Daily Metformin Hydrochloride Sustained-Release Tablets

The objective of this study was to develop once-daily metformin hydrochloride sustained-release tablets (MHSRT) and evaluate their in vitro release behavior. MHSRT were prepared by the film coating method. The in vitro drug release rate of MHSRT and the commercial tablets Fortamet? made in the United States of America in water was fitted with zero order kinetic equation, and Ritger-Peppas kinetic equation in 0.1 M HCl and pH 6.8-phosphate buffer, respectively. The similarity factor f2 values of MHSRT in three different dissolution medium were 82, 80 and 74, respectively in comparison with imported Fortamet?, which were all greater than 50. The results of storage-stability showed that MHSRT were stable for at least 6 months under stress condition (40℃ ± 2℃, RH 75% ± 5%). Therefore, in this study, MHSRT were successfully prepared using optimized formulation technologies that meet mass produce. The in vitro release behavior of MHSRT was almost similar to that of imported Fortamet?.

Effect of nonionic surfactants in release media on accelerated in-vitro release profile of sirolimus eluting stents with biodegradable polymeric coating

It is a well-known fact that sirolimus(SRL) undergoes degradation process via hydrolysis in aqueous media, leading to incorrect assessment of drug amount and thus release characteristics of formulations.The main objective of the present study was to evaluate the effect of nonionic surfactants in media on invitro release profiles for sirolimus eluting stents(SES) coated with biodegradable polymeric matrix.Phosphate buffer and acetate buffer incorporating nonionic surfactants with varying concentrations were examined for adequate solubility and stability(by RP-HPLC). Good sink condition was achieved in phosphate buffer(at pH 4.0) with 1.0% Tween 20, 1.0% Brij 35% and 0.5% Brij 58. Hydrodynamic size(by DLS) and the micelle-water partition coefficient(P) with standard free energy of solubilization(ΔGs°) of drug were evaluated to get some understanding about the solubilization phenomena. About 80% of drug release during the period of 48 h was achieved in optimized drug release media which was 1.0% Tween20 in phosphate buffer pH 4.0. The obtained accelerated SRL release profile in optimized medium correlated well with the real time in-vitro release in phosphate buffer(pH 7.4). Surface morphology changes(by SEM), changes in gravimetric weights and molecular weight change(by GPC) were examined before and after drug release to understand the drug release mechanism which explains that the polymer did not undergo degradation during the drug release.

Release of Nestorone from Biodegradable Rods System in vitro

To study the controlled effect of poly （lactic acid） （PLA）, poly lactic-coglycolic （PLGA） and ethylenediamine （EDA）-maleic anhydride （MAH） modified PLA （EMPLA） for in vitro release of nestorone, rods were prepared using the solvent evaporation method. Amount of drug release in vitro was determined by UV spectrophotometry. Effects of rods diameter, the molecular weight of PLA, the drug percentage and the hydrophilicity of polymers on the release of biodegradable nestorone rods in vitro were investigated. It is indicated that the controlled effect of the biodegradable rods for the release of nestorone in vitro is good. The amount of drug released every week from rods in different diameter is similar to one another. The amount of drug released every week and the accumulative drug released during 12 week were almost in direct proportion with the drug percentage of the rods. The amount of drug released every week is increased as the decreasing of PLA molecular weight. As the hydrophlicity of polymer is improved, the rate of drug release every week is accelerated. The studies show that the plausibility of controlled release of nestorone from PLA, PLGA and EMPLA rods imply the possibility of their application as a controlled delivery system for nestorone. The results show that the greater the molecular weight of PLA is, the slower its degradation is and the slower the drug released; the greater the percentage of nestorone is, the more quickly the drug release. An increase of the hydrophilicity of the polymers will increase their degradation rate and leads to a fast drug release. Anyhow, these rods systems should be further evaluated in vivo.

HPLC Method for the Determination of Tamsulosin Hydrochloride in Sustained Release Tablets

The development and validation of an isocratic high performance liquid chromatographic method is described for the determination of tamsulosin hydrochloride in sustained release tablets. The determination was performed on a Diamonsil BDS C18 column with a mobile phase consisting of a mixture of acetonitrile, methanol and 0 5% phosphoric acid solution (20∶30∶50, V/V/V ) at a flow rate of 1 0 mL/min. UV detection was made at 274 nm. The linear range for tamsulosin hydrochloride was 0 81-8 10 μg/mL. The mean recovery was 99 8% ( S R=0 7%, n =9), and the precision was found to be 0 45% ( n =9). The proposed method can be used for routine analysis of tamsulosin hydrochloride in sustained release tablets.

FACTORS AFFECT THE RELEASE OF PSEUDOEPHDRINE HYDROCHLORIDE FROM THE UNCOATED CATION EXCHANGE RESIN-BASED DRUG DELIVERY SYSTEM IN VITRO

In this paper, it was investigated that the effect of parameters such as the ionic strength, pH, counter-ion type of release medium, particle size, and cross linkage of cation exchange resin on the release of model drug pseudoephedrine hydrochloride (PE) from uncoated drug-resin complex. The drug-resin complex was prepared by the reaction of PE with strongly acidic cation exchange resin (001×4, 001×7, 001×14). The result showed that the loading of PE increased with the increase of temperatures. The release of PE from drug-resin complex at 37℃ was monitored in vitro. From the experiments, it was found that the release rate of PE depends on the pH, composition of the releasing media, increased at lower pH media or with increase of ionic strength of media. Moreover, the release rate of PE was inversely proportional to the cross-linkage and particle size of the cation exchange resin.

Formulation and <i>In-Vitro</i>Release Pattern Study of Gliclazide Matrix Tablet

In current decade, pharmaceutical industries of Bangladesh are giving much emphasize on the formulation of time release preparation to treat various chronic diseases in order to decrease the frequency of administration and to improve patient compliance. Objectives: The objective of this investigation is to design and evaluate sustained release matrix tablet of Gliclazide by direct compression method employing polymers of hydroxypropylmethyl cellulose (HPMC) derivatives (K15M CR and K4M CR) and to select the optimized formulations and compression process by performing a comparative release kinetic study with a reference product, Diamicron MR (one of the worldwide brand of Gliclazide sustain released tablet manufactured by Servier one of the French pharmaceutical company) tablet. Methods: Release kinetics of Gliclazide matrix tablets were determined using USP paddle method at Phosphate buffer (pH 7.4). The release mechanism was explored and explained with zero order, first order, Higuchi and Korsmeyer model. Result: It is found that formulation with lower polymeric concentration follows Higuchi release kinetics and that the formulation with higher concentration best fits with zero order release kinetics. Among the formulations, F1 and F6 show almost similar dissolution profile with Diamicron MR Tablet, which can be suitable candidates for further in-vivo bioequivalence study. Conclusion: Findings of this investigation suggest that F1 and F6 formulations are potential candidates for further bioequivalence study among other formulations.

HPLC法测定参蒲益智缓释胶囊中人参皂苷Rg_(1)、Re、Rd含量

目的采用HPLC对参蒲益智缓释胶囊中人参皂苷Rg_(1)、Re、Rd进行含量测定。方法采用C_(18)色谱柱进行,梯度洗脱,流动相为乙腈(A)-0.1%磷酸溶液(B),检测波长为203nm,流速为1.0 mL·min^(-1),柱温为30℃。结果人参皂苷Rg_(1)、Re、Rd分别在2.00~20.00μg·mL^(-1)、3.00~30.00μg·mL^(-1)、5.00~50.00μg·mL^(-1)浓度范围内线性关系良好。结论该方法简单、稳定,可用作参蒲益智缓释胶囊中3种人参皂苷的含量测定。

HPLC法测定参蒲益智缓释胶囊中β-细辛醚含量

目的 采用HPLC法对参蒲益智缓释胶囊中β-细辛醚含量进行测定。方法 采用C_(18)色谱柱,流动相为甲醇∶0.1%磷酸水溶液(65∶35),检测波长为257nm,流速1.0m L·min^(-1),柱温30℃。结果 β-细辛醚在4.00~40.00μg·m L^(-1)浓度范围内线性关系良好,标准曲线方程为y=192930x-149252(R^(2)=0.9989),平均回收率为99.69%(RSD=0.89%)。结论 该方法简单、稳定、可靠,可用作参蒲益智缓释胶囊中β-细辛醚的含量测定。

Chlorogenic acid loaded chitosan nanoparticles with sustained release property,retained antioxidant activity and enhanced bioavailability

In this study,chlorogenic acid(CGA),a phenolic compound widely distributed in fruits and vegetables,was encapsulated into chitosan nanoparticles by ionic gelation method.The particles exhibited the size and zeta potential of 210 nm and 33 mV respectively.A regular,spherical shaped distribution of nanoparticles was observed through scanning electron microscopy(SEM)and the success of entrapment was confirmed by FTIR analysis.The encapsulation efficiency of CGA was at about 59%with the loading efficiency of 5.2%.In vitro ABTS assay indicated that the radical scavenging activity of CAG was retained in the nanostructure and further,the release kinetics study revealed the burst release of 69%CGA from nanoparticles at the end of 100th hours.Pharmacokinetic analysis in rats showed a lower level of Cmax,longer Tmax,longer MRT,larger AUC0et and AUC0e∞for the CGA nanoparticles compared to free CGA.Collectively,these results suggest that the synthesised nanoparticle with sustained release property can therefore ease the fortification of food-matrices targeted for health benefits through effective delivery of CGA in body.

Preparation and evaluation of sustained-release diltiazem hydrochloride pellets

In this study,diltiazem hydrochloride(DTZ)pellets were prepared successfully by extrusionespheronization method.Then methacrylic acid and ethylcellulose coating formulations were employed to make the DTZ pellets sustained release.The pellets with different coatings were investigated by in vitro dissolution tests.At last,the pellets with the best coating copolymer were subjected to pharmacokinetic studies in beagle dogs.The dissolution profiles of pellets coated with Eudragit
NE30D were similar to Herbesser
,one of the marketed sustained release capsules.In the bioavailability study,the principal pharmacokinetic parameters of self-made pellets and the marketed ones were comparable;the relative bioavailability of DTZ sustained release capsules compared with Herbesser
was 98.5
36.4%.All the data indicated self-made sustained pellets could prolong the release of DTZ,decrease the fluctuation of drug level in vivo,and increase the compliance of patients.