Effect of processing parameters on the formation of spherical multinuclear microcapsules encapsulating peppermint oil by coacervation

The gelatin/gum arabic multinuclear microcapsules encapsulating peppermint oil were prepared by coacervation. The effect of various processing parameters, including the core/wall ratio, wall material concentration, pH value, as well as stirring speed on the morphology, particle size distribution, yield and loading was investigated. When the wall material concentration or the core/wall ratio increased, the morphology of multinuclear microcapsules changed from spherical to irregular and the average particle size increased, the optimal wall material concentration and the core/wall ratio were 1% and 2:1, respectively. The multinuclear spherical microcapsules with desired mean particle size can be manufactured by modulating the pH value and stirring speed. The ideal preparation conditions were pH 3.7 at 400?rpm of stirring speed. The yield of multinuclear microcapsules encapsulating peppermint oil by coacervation was ～90% and the processing parameters had very slight influence on the yield. When transglutaminase was used as the cross-linker instead of formaldehyde, morphology, mean particle size, yield and loading remained the same as that hardening with formaldehyde, but the particle size distribution became narrower.     

Evaluation of ketorolac tromethamine microspheres by chitosan/gelatin B complex coacervation

Microspheres (MS) of Ketorolac Tromethamine (KT) for oral delivery were prepared by complex coacervation (method-1) and simple coacervation (method-2) methods without the use of chemical crossalinking agent (glutaraldehyde) to avoid the toxic reactions and other undesirable effects of the chemical cross-linking agents. Alternatively, ionotropic gelation was employed by using sodium-tripolyphosphate (Na-TPP) as cross linking agent. Chitosan and gelatin B were used as polymer and copolymer respectively. All the prepared microspheres were subjected to various physico-chemical studies, such as drug-polymer compatibility by Thin Layer Chromatography (TLC) and Fourier Transform Infra Red Spectroscopy (FTIR), surface morphology by Scanning Electron Microscopy (SEM), frequency distribution, encapsulation efficiency, in-vitro drug release characteristics and release kinetics. The physical state of drug in the microspheres was determined by Differential Scanning Calorimetry (DSC) and X-ray powder Diffractometry (XRD). TLC and FTIR studies indicated no drug-polymer incompatibility. All the MS showed release of drug by a fickian diffusion mechanism. DSC and XRD analysis indicated that the KT trapped in the microspheres existed in an amorphous or disordered-crystalline status in the polymer matrix. It is possible to design a controlled drug delivery system for the prolonged release of KT, improving therapy by possible reduction of time intervals between administrations.     

Physicochemical characterization and enzymatic degradation of casein microcapsules prepared by aqueous coacervation

The use of biopolymers in sustained release systems has been studied by many research groups because of the bioavailability and biodegradability of these compounds. Casein is a natural biopolymer whose degradation results in biologically utilisable compounds. The objective of the present study was to assess the potential of casein microcapsules (CAS/MC) as sustained release systems using acetaminophen as a model drug. CAS/MC were prepared by aqueous coacervation in lactate buffer containing gelatin, hydroxypropyl cellulose (HPC) and lecithin. After preparation, the microcapsules were treated, or not, with glutaraldehyde as a cross-linking agent. CAS/MC were loaded using two distinct procedures, either by dissolving 50% of the drug (w/w), relative to casein, in the polymer dispersion or by dissolving the drug in the coacervating solution. The drug present in CAS/MC was quantified by HPLC after an enzymatic degradation assay, and the CAS/MC were analysed by scanning electron microscopy and thermal analysis (differential scanning calorimetry and thermogravimetrical analysis). Loading of the drug was ~ 8% (w/w), with high resistance to enzymatic attack. The absence of an acetaminophen melting peak indicated that there was no drug present on the surface of the cross-linked systems. In addition, loading was accompanied by a reduction of the specific heat capacity of the systems, which suggests a decrease in stability. The outer morphology of the encapsulating polymer was affected by the process of microencapsulation. The data suggest that the microencapsulation process of aqueous coacervation and cross-linking is appropriate for the preparation of microencapsulated systems for sustained drug delivery.     

Influence of pH on the benzodiazepine-human serum albumin complex

Summary The influence of pH on the binding of benzodiazepine derivatives to HSA was studied by circular dichroism measurements and by gel filtration.The binding of nearly all benzodiazepines is increased by rising the pH from 6.60 to 8.20. For flurazepam, clonazepam, and nitrazepam this increase in binding is due to an increase of the affinities, while for the other substances the affinity remains constant and the number of binding sites is increased from one to two. The changes in binding of the benzodiazepines by rising the pH are explained by a cationic amino acid residue near or at the benzodiazepine binding site of the HSA molecule. This second binding site is not detectable by circular dichroism. For several of the substances rising the pH from 6.60 to 8.20, is accompanied by large alterations of the optical properties of the HSA-benzodiazepine complexes. These alterations are explained by changes of the asymmetric environment of the benzodiazepine binding site at the HSA molecule in the structural transition at slightly alkaline pH values. To explain the different reactions of the benzodiazepines within the NB transition a theory is given.Supported by a grant of the Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg.     

不同pH的溶出介质对HPMC骨架片释药的影响

目的探讨溶出介质的pH对难溶性药物的HPMC骨架片释药的影响.方法以甲氧苄胺嘧啶、卡马西平、磺胺甲恶唑和茶碱四种难溶型性药物为模型药物,测定四种pH缓冲溶液介质(pH1.0,pH4.0,pH6.0,pH7.5)下的药物的溶解度和释放度.结果难溶性药物的HPMC骨架片释药随着其溶解度的增加而加快.结论难溶性药物HPMC骨架片释药的差异主要与药物在不同pH的溶出介质中的溶解度有关.     

明胶纤维网粘附性及生物吸收性的实验研究

目的 通过对明胶纤维网在出血创面粘附性能及生物吸收性能的研究,为临床应用和实验研究提供依据。方法 在兔背部取中厚皮片,造成均匀的出血创面,将明胶纤维网（GF）、氧化纤维素（OC）和明胶海绵（GL）三种局部止血材料随机贴敷于渗血创面,4种压力分别压30秒后,用张力换能器垂直向上牵引,二道生理记录仪描记粘附力（g/cm2）;将GF15mg埋入兔肝右叶后,分别于24小时、3天和 1,3,4,8周在埋药部位取标本,观察组织吸收及局部反应。结果 GF和OC与创面的粘附力显著大于GL（P<0.01）,GF随压力的增加粘附力逐渐增大,与OC,GL比较有显著差异（P<0.01）,GF对组织的反应较轻,8周时即可大部分吸收。结论 GF,OC与创面粘附力大于GL,增大压力可以增强GF的粘附力,证明GF是一种止血效果好、组织反应轻、可吸收的止血材料。     

HPLC法同时测定楚雄臭菜中槲皮素和山奈酚的含量

目的建立HPLC法测定楚雄臭菜中的槲皮素和山奈酚含量的方法。方法采用色谱柱:InertSustain C18(250 mm×4.6 mm,5μm);以乙腈(A)-0.3%磷酸水溶液(B)为流动相进行梯度洗脱;流速:0.8 m L/min;检测波长:360 nm;柱温:30℃。结果槲皮素的进样量在0.034~0.272μg范围内(r=0.999 9)、山奈酚的进样量在0.039~0.317μg范围内(r=0.999 8)线性关系良好,槲皮素、山奈酚的平均回收率分别为99.33%(RSD=1.33%,n=6)、99.48%(RSD=1.85%,n=6)。结论本方法操作简便、快捷,稳定性高,重现性好,为楚雄臭菜药材的质量评价提供依据。     

双氯芬酸钠明胶微球的制备及体内外释药的研究

目的将双氯芬酸钠制备成明胶微球,考察其缓释效果。方法采用单凝聚法制备双氯芬酸钠明胶微球,并对微球的体内外释药进行考察。结果制备的微球粒径范围为48～100μm,平均粒径为70.70±11.29μm,载药量为35%。体内外释药实验结果表明双氯芬酸钠明胶微球有缓释作用。结论本法制备的双氯芬酸钠明胶微球能够起到明显缓释作用。     

PH对尼扎替丁注射液稳定性的影响

目的考察不同pH对尼扎替丁注射液稳定性的影响。方法将不同pH的样品分别经100℃、30min灭菌、室温放置10d和60℃放置10d处理后,采用HPLC测定供试品含量和有关物质的变化。结果和结论建立了尼扎替丁注射液的含量测定和有关物质检查法,认为样品在pH6.0～7.0间较稳定。     

Preparation of microcapsules with narrow-size distribution by complex coacervation: Effect of sodium dodecyl sulphate concentration and agitation rate

In this paper, microcapsules with narrow-size distribution, in which the core materials are a kind of suspension containing pigment scarlet powders dispersed in dyed tetrachloroethylene with Span-80 as an emulsifier, are prepared by complex coacervation through controlling sodium dodecyl sulphate (SDS) concentration and agitation rate. The microcapsules, formed in optimized process of 0.01 wt% SDS and 800 rpm, are ～40 μm in diameter. The phase diagram for the gelatin/SDS/water system indicates that the concentration of SDS in the experiments is outside of the complex formation zone to form a gelatin–SDS complex. Consequently, SDS preferential adsorbs and enriches on the surface of the core droplets due to its higher surface activity. Then, gelatin deposits with SDS at the core droplet/water interface to form a primary layer of complexation. Subsequently, with the pH lower than the isoelectric point of gelatin, complex coacervate of gelatin and gum arabic grows on the primary layer surface and finally deposits on the droplets to form a secondary layer. On the whole, the research indicates that the existence of SDS not only decreases the droplet diameters and centralizes the droplets size distribution, but also accelerates coacervation of gelatin and gum arabic to reach the core droplet/water interface, forming no aggregating microcapsules.     

Influence of pH on the cytotoxic activity of chlorambucil

The cytotoxic activity of chlorambucil as a function of pH was investigated in P388 tumor cells growing in static suspension culture. A decrease in extracellular pH from 7.8 to 7.2 was associated with a decrease in intracellular pH from 7.92 to 7.55. The cytotoxic potency of chlorambucil increased as the extracellular pH decreased; IC99 values were 20 and 60 microM when the extracellular pH was 7.2 and 7.8 respectively. Covalent binding to cellular macromolecules was about 1.9 times greater at pH 7.2 relative to that at pH 7.8. These results suggest that pH may be an important determinant of the oncotoxic specificity of chlorambucil, and that the cytotoxic activity of this agent could be selectively directed toward tumor cells by the selective manipulation of intracellular and extracellular pH. A potential influence of intracellular and extracellular pH on cytotoxic, mutagenic, carcinogenic, and teratogenic potencies of other chemicals is also suggested. Additionally, these investigations demonstrate the importance of carefully controlling pH throughout the drug exposure period when evaluating the relative potency of potential cytotoxic, mutagenic, carcinogenic, and teratogenic agents in cell or organ culture.     

Impact of crystalline form changing on behavior of microcapsules prepared from three-component gel system

In this paper, the effect of anhydrous-monohydrate process-induced transformation of theophylline was examined in microcapsules produced by in situ gelation method using sodium alginate, hydroxypropylmethylcellulose and hydroxyethylcellulose. Films produced from gel were applied to characterize the changes by NIR spectroscopy, X-ray, DSC method and stereomicroscopy because it is easier to study that in films in the case of gel systems used in situ gelation process. The properties of end-product are influenced by the swelling ability, equilibrium water uptake, release profile and encapsulation efficiency. Water penetration and drug release were evaluated by Davidson-Peppas and Korsmeyer-Peppas models. The ex tempore formed monohydrate crystals were smaller and built into the matrix structure in a greater extent. Increased drug release, matrix erosion and diffuse reflectance values at 1470 and 1950?nm were observed added theophylline later into the gel because of developing a denser structure.     

Effect of pH on poppy seed 10S protein

The effect of acid pH on the 10S protein of poppy seed has been studied by ultracentrifugation, polyacrylamide gel electrophoresis, turbidity, and difference, fluorescence and circular dichroism spectra. The protein dissociated into lower molecular weight fractions in the pH range of 4.0 down to 2.5 judged by ultracentrifugation, electrophoresis and turbidity measurements. U.v. difference spectra and fluorescence measurements suggested denaturation of the protein. Thus, both dissociation and denaturation occurred down to pH 2.5. At more acid pH values (pH 1.3), reassociation and refolding probably occurred. Circular dichroism studies showed a large increase in the amplitude of the peak at pH values of 2.8 and 1.3 indicating that unordered structures are formed at acid pH values.     

Influence of drug partition coefficient and pH value of sink solution on permeation from porous thick-walled ethyl cellulose microcapsules

The permeation of barbitone sodium, benzoic acid, and salicylic acid from microcapsules into aqueous medium has been examined at different pH values. The apparent diffusion coefficients of drugs were linearly proportional to the ethyl cellulose/water partition coefficient of drugs, and the straight line parameters were dependent upon volume fractions of water-filled pores (i.e. capsule size), testifying to a previously proposed mechanism of drug permeation. The rate of drug permeation was also a function of the pH-value of the surrounding sink solution; the period of zero order release was longer at low pH because of the change of drug partition or solubility or both.     

pH值对磺胺嘧啶银乳膏稳定性的影响

目的:考察不同pH值的磺胺嘧啶银乳膏稳定性.方法:观察不同厂家的硬脂酸配制的磺胺嘧啶银乳膏外观变化及不同pH值的磺胺嘧啶银乳膏的外观变化.结果:pH＜8.0时,磺胺嘧啶银乳膏的稳定性较好.结论:磺胺嘧啶银乳膏应检查其pH值.     

An Unexpected pH Effect on the Stability of Moexipril Lyophilized Powder

Because of the limited stability of moexipril (RS-10085; 1) in aqueous solution, lyophilized parenteral formulations were evaluated as a function of pH in this study. In general, the lyophilized powder of 1 showed about two orders of magnitude less reactivity at 50°C than in aqueous solution at pH values below 3 or above 6. At pH 5.1, however, the lyophilized powder had maximum reactivity, with the rate actually comparable to that observed in aqueous solution. When the distribution of the two major products, diketopiperazine (DKP) 2 and ester hydrolysis analogue 3, was compared to the observed kinetics as a function of pH, it was clear that removal of water via lyophilization suppressed the spontaneous k ₁ cyclization process, the spontaneous k ₃ hydrolysis process, and the specific base-catalyzed k ₄ hydrolysis process. The overall spontaneous k ₂ cyclization process, however, was not affected by lyophilization. The latter result is accounted for by the increased equilibrium constant for the formation of the tetrahedral intermediate, To, as a result of lyophilization. This study demonstrates that stability data in solution can not be used for predicting the stability of moexipril in lyophilized powder form.     

Effects of pH and Dose on Nasal Absorption of Scopolamine Hydrobromide in Human Subjects

Purpose. The present study was conducted to evaluate theeffects of formulation pH and dose on nasal absorption of scopolaminehydrobromide, the single most effective drug available for the prevention ofnausea and vomiting induced by motion sickness. Methods. Human subjects received scopolamine nasally at adose of 0.2 mg/0.05 mL or 0.4 mg/0.10 mL, blood samples were collected atdifferent time points, and plasma scopolamine concentrations were determinedby LC-MS/MS. Results. Following administration of a 0.2 mg dose, theaverage C_max values were found to be 262 ± 118, 419± 161, and 488 ± 331 pg/mL for pH 4.0, 7.0, and 9.0formulations, respectively. At the 0.4 mg dose the average C_maxvalues were found to be 503 ± 199, 933 ± 449, and 1,308± 473 pg/mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At a0.2 mg dose, the AUC values were found to be 23,208 ± 6,824, 29,145± 9,225, and 25,721 ± 5,294 pg.min/mL for formulation pH 4.0,7.0, and 9.0, respectively. At a 0.4 mg dose, the average AUC value wasfound to be high for pH 9.0 formulation (70,740 ± 29,381 pg.min/mL)as compared to those of pH 4.0 (59,573 ± 13,700 pg.min/mL) and pH 7.0(55,298 ± 17,305 pg.min/mL) formulations. Both the C_maxand AUC values were almost doubled with doubling the dose. On the otherhand, the average T_max values decreased linearly with a decreasein formulation pH at both doses. For example, at a 0.4 mg dose, the averageT_max values were 26.7 ± 5.8, 15.0 ± 10.0, and 8.8± 2.5 minutes at formulation pH 4.0, 7.0, and 9.0, respectively. Conclusions. Nasal absorption of scopolamine hydrobromidein human subjects increased substantially with increases in formulation pHand dose.     

浅析PH值对药品鉴别试验结果的影响

本文从样品取用量,试剂取用量,药物性质三方面分析了试验环境的ＰＨ值对鉴别试验结果的影响。     

基质pH及促渗剂对阿昔洛韦水凝胶贴剂体外透皮性能的影响

分别制备了基质pH为5.0、6.0、7.5的不含促渗剂的阿昔洛韦水凝胶贴剂,在基质pH 6.0的处方中加入不同浓度的月桂氮革酮、Ⅳ.甲基吡咯烷酮(NMP)、薄荷醇、吐温-80、聚乙二醇(PEG)400作为促渗荆,以考察基质pH及促渗剂对阿昔洛韦透过离体小鼠皮肤的影响.结果表明,基质pH升高,阿昔洛韦的透皮速率增大.与不含促渗剂的基质pH6.0处方组对照,NMP、PEG 400单用不能提高阿昔洛韦的渗透速率,4%的吐温-80、薄荷醇和月桂氮革酮均可提高阿昔洛韦的经皮渗透.     

pH对盐酸美普他酚鼻腔吸收的影响

目的研究盐酸美普他酚制剂中pH和鼻腔吸收之间的关系.方法通过鼻腔在体循环试验考察不同pH环境对盐酸美普他酚鼻腔吸收的影响,并利用体内试验考察模型药物经鼻入脑的情况.结果鼻腔在体循环试验发现盐酸美普他酚在碱性条件下吸收显著优于酸性条件,但是在体内试验中发现不同pH环境对药物吸收入脑并没有显著性差异.结论制剂中的pH环境对盐酸美普他酚鼻腔吸收和入脑无显著影响.