Development of a microencapsulated form of cefuroxime axetil using pH-sensitive acrylic polymers

Abstract

Cefuroxime axetil (CA) was encapsulated in pH-sensitive acrylic micro spheresin order to formulate a suspension dosage form. Using this microencapsulated form it was expected to prevent leaching of the drug from the micro spheresinto the suspension medium and to assure the release of the drug in the first part of the intestinethus avoiding changes to its bioavailability. For this purpose CA was microencapsulated within several types of acrylic polymers by the solvent evaporation and the solvent extraction techniques., The acrylic polymers selected were: Eudragit E (positively charged and soluble at pH 5)Eudragit L-55 (negatively charged and soluble at pH >5.5) and Eudragit RL (neutralinsolublebut readily permeable)., The influence of the polymer electrical charge on the stability and in vitro release of CA was investigated., Though Eudragit E micro spherespresented good morphological characteristics and dissolution behaviourthe analysis of the stability of CA in the presence of Eudragit E by HPL Cindicated a negative interaction between both compounds., Howeverformulations made of Eudragit L-55 and RL in the ratios 100:0 and 90:10 were adequate in terms of the stability of the encapsulated CA., The dissolution studies showed a critical pH between 5.2 and 6.0which allowed the complete release of CA in a short period., Furthermorethese polymer micro sphereswere shown to be efficient in masking the taste of CA.     

Slow release polymer-drug systems obtained by moisture promoted polyreactions. 1. Codeine resinate encapsulated in poly(alkyl α-cyanoacrylates)

Abstract

Samples of codeine resinate consisting of a carboxylic cation exchanger (as a polymeric carrier) and codeine (as a drug) were coated with poly(alkyl α-cyanoacrylates) by suspending and stirring wet resinate beads in a toluene solution of the monomer. Methyl, ethyl and n-butyl α-cyanoacrylates were used as monomers. Each coated material released codeine more slowly than the non-coated. The data obtained confirmed that water promoted the polymerization of alkyl α-cyanoacrylates, which proceeded at the surface of the wet resinate beads. The rate of codeine release depended on the type of monomer used for coating, the monomer/resinate feed ratio and the plymerization time.     

Considerations for the development of health-based surface dust cleanup criteria for beryllium

Abstract

The exposure–response patterns with beryllium sensitization (BeS), chronic beryllium disease (CBD) and lung cancer are influenced by a number of biological and physicochemical factors. Recent studies have suggested dermal exposure as a pathway for BeS. In light of the current non-health-based DOE Beryllium Rule surface criteria, the feasibility of deriving a human health-based surface dust cleanup criteria (SDCC) for beryllium was assessed based on toxicology and health risk factors via all potential routes of exposure. Beryllium-specific and general exposure factors were evaluated, including (1) beryllium physicochemical characteristics, bioavailability and influence on disease prevalence, and (2) chemical dissipation, resuspension and transfer. SDCC for non-cancer (SDCC_NC) and cancer (SDCC_CA) endpoints were derived from a combination of modern methods applied for occupational, residential and building reentry surface dust criteria. The most conservative SDCC_NC estimates were derived for dermal exposure (5–379?μg/100?cm² for 0.1–1% damaged skin and 17–3337?μg/100?cm² for intact skin), whereas the SDCC_CA for inhalation exposure ranged from 51 to 485?μg/100?cm². Considering this analysis, the lowest DOE surface criterion of 0.2?μg/100?cm² is conservative for minimizing exposure and potential risks associated with beryllium-contaminated surfaces released for non-beryllium industrial or public sector use. Although methodological challenges exist with sampling and analysis procedures, data variability and interpretation of surface dust information in relation to anthropogenic and natural background concentrations, this evaluation should provide useful guidance with regard to cleanup of manufacturing equipment or remediation of property for transfer to the general public or non-beryllium industrial facilities.     

Formulation and in vitro evaluation of a PEGylated microscopic lipospheres delivery system for ceftriaxone sodium

The aim of this study was to formulate and evaluate in vitro, ceftriaxone sodium lipospheres dispersions for oral administration. Ceftriaxone sodium lipospheres were prepared by melt-emulsification using 30%w/w Phospholipon^® 90H in Softisan^® 154 as the lipid matrix containing increasing quantities of PEG 4000 (10, 20, 30, and 40%w/w). Characterization based on particle size, particle morphology, encapsulation efficiency, loading capacity and pH were carried out on the lipospheres. Microbiological studies of the ceftriaxone sodium-loaded lipospheres were performed using Escherichia coli as the model organism. In vitro permeation of ceftriaxone sodium from the lipospheres through artificial membrane (0.22?μm pore size) was carried out using Franz cell and simulated intestinal fluid (SIF) without pancreatin as acceptor medium. Photomicrographs revealed spherical particles within a micrometer range with minimal growth after 1 month (Maximum size?=?64.76?±?3.81?μm). Microbiological studies indicated that lipospheres formulated with 20%w/w of PEG 4000 containing 2%w/w or 3%w/w of ceftriaxone sodium gave significantly (p?<?0.05) higher inhibition zone diameter than those with 30%w/w or 40%w/w of PEG 4000. The result also indicated that lipospheres with 10%w/w PEG 4000 resulted in significantly higher encapsulation efficiency (p?<?0.05) while those with 30%w/w gave the least, while the loading capacity values ranged from 3.22?mg of ceftriaxone sodium/100?mg of lipid to 6.36?mg of ceftriaxone sodium/100?mg of lipid. Permeation coefficient values varied and ranged from 8.55?×?10^?7 cm/s to 2.08?×?10^?6 cm/s depending on the concentration of PEG 4000. The result of this study gave insight that the issue of ceftriaxone stability in oral formulation could be adequately addressed by tactical engineering of lipid drug delivery systems such as lipospheres.     

Preparation of N,O-carboxymethyl chitosan nanoparticles as an insulin carrier

The aim of this research was to develop pH-sensitive insulin-loaded NOCC (N,O-carboxymethyl chitosan) nanoparticles for the controlled release of insulin via the oral route. Thus, in this study, insulin-loaded NOCC nanoparticles were prepared by ionic gelation of NOCC with TPP (tripolyphosphate). NOCC nanoparticles were formed at conditions of 2?mg/ml of NOCC and 1?mg/ml of TPP. It was found that the encapsulation efficiency and process yield decreased with increasing NOCC to TPP weight ratio. Furthermore, the cumulative release of insulin from insulin-loaded NOCC nanoparticles decreased with decreasing NOCC-to-TPP weight ratio, but it increased with decreasing the initial concentration of insulin. The higher the pH of the phosphate buffered saline, the greater the amount of cumulative release of insulin-loaded NOCC nanoparticles, and thus they could protect insulin from acid.     

Solid lipid nanoparticles for ocular drug delivery

Ocular drug delivery remains challenging because of the complex nature and structure of the eye. Conventional systems, such as eye drops and ointments, are inefficient, whereas systemic administration requires high doses resulting in significant toxicity. There is a need to develop novel drug delivery carriers capable of increasing ocular bioavailability and decreasing both local and systemic cytotoxicity. Nanotechnology is expected to revolutionize ocular drug delivery. Many nano-structured systems have been employed for ocular drug delivery and yielded some promising results. Solid lipid nanoparticles (SLNs) have been looked at as a potential drug carrier system since the 1990s. SLNs do not show biotoxicity as they are prepared from physiological lipids. SLNs are especially useful in ocular drug delivery as they can enhance the corneal absorption of drugs and improve the ocular bioavailability of both hydrophilic and lipophilic drugs. SLNs have another advantage of allowing autoclave sterilization, a necessary step towards formulation of ocular preparations. This review outlines in detail the various production, characterization, sterilization, and stabilization techniques for SLNs. In-vitro and in-vivo methods to study the drug release profile of SLNs have been explained. Special attention has been given to the nature of lipids and surfactants commonly used for SLN production. A summary of previous studies involving the use of SLNs in ocular drug delivery is provided, along with a critical evaluation of SLNs as a potential ocular delivery system.     

Nanoparticle-based immunopotentiation via tetanus toxoid-loaded gelatin and aminated gelatin nanoparticles

Gelatin nanoparticles (GNPs) and aminated gelatin nanoparticles (AGNPs) were prepared and used as an adjuvant to improve the delivery of tetanus toxoid (TT). Nanoparticles were characterized in vitro for their size, shape, entrapment, and release. TT-FITC conjugate was used to determine entrapment and release from nanoparticles. The immune-stimulating activity was studied by measuring anti-TT IgG, IgG1, and IgG2a isotype and cytokine responses following subcutaneous (s.c) injection of nanoparticles in BALB/c mice and was compared with alum-TT vaccine. Gelatin and aminated gelatin (AG) specific IgG response was also determined. Both GNPs and AGNPs demonstrated comparable IgG response and a significantly higher (p?<?0.05) cytokine response (IL-2 and IFN γ) as compared to alum-TT vaccine. Nanoparticulate formulations elicited both Th1 and Th2 responses and induced negligible undesirable immunogenicity against the carrier, as demonstrated by lower level of gelatin and AG-specific IgG response as compared to control.     

Gastroretentive hydrodynamically balanced systems of ofloxacin: In vitro evaluation

Hydrodynamically balanced systems (HBSs) of ofloxacin were prepared using lactose, HPMC K4M, PVP K 30, and liquid paraffin, which may increase the mean residence time in the gastrointestinal tract, and may be able to provide maximum drug at the site of absorption to improve oral bioavailability. All these formulated HBS capsules were floated well over 6 h with no floating lag time. They also showed sustained drug release over 6 h. Time for 50% release of ofloxacin was within the range, 2.47 ± 0.02 to 3.07 ± 0.08 h. The in vitro drug release from these HBS capsules was dependent on HPMC K4M, PVP K 30, and liquid paraffin content. The drug release pattern of these HBS capsules containing ofloxacin followed the Higuchi model with the anomalous transport mechanism.     

Effect of risperidone on the fluoxetine-induced changes in extracellular dopamine,serotonin and noradrenaline in the rat frontal cortex

BackgroundSeveral clinical reports have documented a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants, in particular selective serotonin reuptake inhibitors, in the treatment of drug resistant depression. The aim of our study was to understand the mechanism of the clinical efficacy of a combination of fluoxetine (FLU) and risperidone (RIS) in drug-resistant depression.We studied the effect of FLU and RIS, given separately or jointly on the extracellular levels of dopamine (DA), serotonin (5-HT) and noradrenaline (NA) in the rat frontal cortex.MethodsAnimals were given single intraperitoneal injections of RIS at a doses of 0.1 or 1 mg/kg and FLU at a dose of 10 mg/kg. The release of DA, 5-HT and NAin the rat frontal cortex was investigated using microdialysis in freely moving animals. The extracellular level of DA, 5-HT and NA was assayed by HPLC with coulochemical detection.ResultsRIS (0.1 and 1 mg/kg) and FLU (10 mg/kg) increased the extracellular level of cortical DA, 5-HT and NA. Co-treatment of both drugs was more effective in increasing DA release than administration of each of the drugs alone at doses of RIS 1 mg/kg and FLU 10 mg/kg. Co-treatment of FLU and RIS 0.1 mg/kg was more potent than FLU alone, while the effect of joint injection of FLU and RIS 1 mg/kg was stronger than RIS 1 mg/kg alone on 5-HT release. The combination of FLU with both doses of RIS was not effective in increasing NA release as compared to drugs given alone.ConclusionsOur data indicate that the effect of the combined administration of RIS and FLU on DA and 5-HT release in the rat frontal cortex may be of crucial importance to the pharmacotherapy of drug resistant depression.     

骨载异烟肼缓释微球的制备及其在动物模型中的释放研究

目的：观察探讨骨载异烟肼聚乳酸微球的设计和制备方法及其在动物模型中的释放效果。方法：选择24只雄性新西兰大白兔作为实验动物模型,采用复乳法制备缓释微球,对微球进行形态学观察、粒径分布观察、体内释药和体外释药观察。结果：平均微球粒径（10.59±0.3）μm,平均包封率（44.9±0.9）%,平均载药率（13.0±0.6）%。在24h、72h、1w、3w微球组滑膜药物浓度明显高于口服组和原药组,P＜0.05。与口服组和原药组对比,微球组0～24h药物波动差值明显更低,P＜0.05。结论：本研究制备的骨载异烟肼缓释微球具有良好的缓释性,能够在抗结核治疗中置入骨结核病灶对术后病灶发挥持久的疗效。