Functionality of protective colloids affecting the formation,size uniformity and morphology of drug-free polylactic acid microspheres

Abstract

Drug-free polylactic acid (PLA) microsphcres were prepared by an emulsitication-solvent evaporation technique using different types of protective colloids. The influence of five types of hydrophilic prolymers (polysaccharides, proteins, synthetic cellulose derivatives, synthetic nonionic polymers and surfactants) on the formation, size uniformity and morphology of PLA microspheres was investigated. Four characteristic functions (surface activity, viscosity, electric charge and interfacial film formation) of the hydrophilic polymer aqueous solutions were used to evaluate the efficacy of these protective colloids used. The results indicate that these four functions were the key parameters to achieve the formation of PLA microspheres. The best protective colloid should have high surface activity, optimum viscosity, adequate electric charge, and form an interfacial film to give a higher recovery, better size uniformity and smoother topography of the PLA microsphcres.     

Enteric Controlled-Release Pantoprazole-Loaded Microparticles Prepared by Using Eudragit S100 and Poly(ε-caprolactone) Blend

Microparticles of poly(ε-caprolactone) and of its blend with Eudragit® S100 were prepared by emulsion/solvent evaporation technique to provide controlled release and gastro-resistance for an acid labile drug. This drug was sodium pantoprazole, a proton pump inhibitor. Both formulations were successfully prepared, but only the microparticles prepared with the blend were capable of stabilizing the drug in the acid medium. Furthermore, this formulation showed in vivo protection of stomachs against ulceration caused by ethanol in rats. These microparticles were tabletted, and the tablets demonstrated slower drug release and higher acid protection than the microparticles before tabletting.     

Content uniformity testing: suitability of different approaches for marketed low dose tablets

Context: Content uniformity (CU) testing was developed and improved to control the effectiveness and safety of dosage units. Many modifications of compendial CU test have been introduced and several alternatives have been suggested.

Objectives: This study aims to evaluate the degree of suitability of current USP CU test for low dose tablets and to compare the performance of the current test with that of the former USP27-NF22 and other alternatives for different sample sizes.

Methods: All locally marketed risperidone (RSP) tablets were analyzed using newly developed and validated isocratic UPLC method. The CU results were statistically analyzed in groups with sample sizes comparable to the USP sampling plans.

Results: Seven out of eleven products failed the different requirements of the former and current USP <905>chapters as well as of several alternative CU tests with several substantial deviations.

Conclusion: The current USP <905> chapter was found to have some deficiencies that allowed such failed products to exist in the market. The dependence of compendial CU test on two-staged sampling plan and the use of arithmetic mean to calculate the reference and acceptance values were obvious shortcomings.     

中药制剂含量均匀度的测定方法初探

以中药制剂含量均匀度研究的必要性为切入点,归纳总结了可用于中药制剂含量均匀度的测定与评估方法,并对机器视觉技术与红外光谱指纹图谱进行了阐述,旨在提升中药制剂品质,保证临床用药的安全、有效,推动适合中药制剂含量均匀度评价体系的建立。     

Influence of a Melt Flow on Generation of Functionally Graded Structure in Bulk Polymeric Materials under Uniaxial Thermal Gradient

A mechanism for the generation of the compositional gradient along the long axis for poly(ε‐caprolactone) (PCL)/poly(ethylene oxide) (PEO) blend under uniaxial thermal gradient was proposed by observations of the convection of polymer using graphite powder as a visual probe. The convection under the thermal gradient promoted the transfer of PCL into the liquid phase from the interface of PEO crystallites. The convex downward shape of the solid–liquid interface indicates the generation of the compositional gradient along the radial direction. By dissolution of PEO, a porous scaffold with a porosity gradient structure along the longitudinal direction was fabricated.

     

Miscibility of Blends of Biodegradable Polymers and Copolymers with Different Plasticizers

Miscibility between components of different plasticizer(A)/solvent(B)/biodegradable polymer(C) ternary systems with H‐bonding has been compared. Systems were formed by two H‐donor phenolic plasticizers, 4‐nonylphenol (NP) and 4:4′‐dihydroxydiphenylmethane (BPF); an H‐acceptor solvent, epichlorohydrin (ECH); and H‐acceptor poly(3‐hydroxybutyrate) (PHB) or poly[(3‐hydroxybutyrate)‐co‐(3‐hydroxyvalerate)] (PHBHV) copolymers. Blend miscibility is the result of the balance of three competitive H‐bondings: plasticizer self‐association (AA), plasticizer‐solvent (AB) and plasticizer‐polymer (AC) interassociations. The strength and extent of such specific interactions have been experimentally monitored by fluorescence spectroscopy either in solution or in solid state. Theoretical modelling has been conducted with a recent thermodynamic approach based on two free‐energy excess functions.

     

Studies of sex pheromone production under neuroendocrine control by analytical and morphological means in the oriental armyworm, Pseudaletia separata, Walker (Lepidoptera: Noctuidae)

Most female moths produce species-specific sex pheromone blends in the modified epidermal pheromone gland (PG) cells generally located between the 8 and 9th abdominal segments. The biosynthesis is often regulated by pheromone biosynthesis activating neuropeptide (PBAN) either in or prior to de novo fatty acid synthesis or at the formation of oxygenated functional group. In Pseudaletia separata, information about life span, calling, PG morphology, daily fluctuation of pheromone production and its hormonal regulation is limited.We measured pheromone titer daily (16:8; L:D) at 2 h intervals in scotophase. Blend ratio stabilized during the 2nd day (till 4-5th) at 6th hour of scotophase, with the ratio of 27.5:12.8:44.4:15.3 for Z-11-16OH:16OH:Z-11-16Ac:16Ac, respectively. Females showed calling behavior from this time. We found with light and fluorescence microscopy that PG consisted of intersegmental membrane (A part), and dorso-lateral region of 9th abdominal segment (B part), encountering for ∼35% of total production revealed by gas chromatography. Ratios did not reveal difference. We did not find precursor (triacylglycerols) accumulation in form of lipid droplets, implying that PBAN stimulates de novo biosynthesis of 16:acyl precursors. In vivoHez-PBAN injections (1-3 × 5 pmol, 2 h intervals) into 3 days old 16-18 h decapitated females stimulated pheromone production, both in A and B parts. Blend analyses including ratios suggest stimulation of the initial phase of synthesis, but desaturation of fatty acyl intermediates do not follow proportionally. More saturated fatty acid is converted from the available pool to the final OH and Ac, compared to females kept intact in scotophase. In vitro studies (PGs incubated 4-6 h in the presence of 0.25 or 0.5 μM Hez-PBAN, especially with surplus 2 mM malonyl-CoA) revealed higher saturated component ratio than the unsaturated, compared to natural blend or in vivo injections.     

An eco-friendly HPLC-UV method for the determination of risedronate in its bulk and tablet dosage form with application to content uniformity,dissolution and stability testing

Risedronate is a nitrogen-containing bisphosphonate for the treatment and prevention of postmenopausal osteoporosis. The current work aims to develop a novel green HPLC-UV method for the rapid analysis of risedronate sodium in bulk and tablet formulation. The analyzed samples were separated on Waters Atlantis dC18 (150 mm × 3.9 mm; 5 μm) column using a green mobile phase consisting of potassium phosphate buffer pH 2.9 and potassium edetate buffer pH 9.5 in a ratio of 1:2, the final pH was adjusted to 6.8 with phosphoric acid, the mobile phase was pumped at a rate of 1.0 mL/min, with column temperature set at 30 °C, eluted samples were detected at 263 nm and the chromatographic run time was 3.0 min. The method was found to be linear over the concentration range of 14–140 μg/mL with a correlation coefficient (r²) of 0.9994. Accuracy and precision were evaluated from three QC samples (LQC, MQC and HQC) together with the five calibrators where the percentage accuracy was found to be 101.84%. Processed quality control samples of risedronate sodium were tested for stability at different conditions, short term, long term and freeze- thaw stability. The current method was further extended to study the content uniformity of Actonel® tablets following United States Pharmacopoeia (USP) guidelines. The proposed method was fully validated as per ICH guidelines.     

一种新的检测磁共振设备主磁场均匀性的设计

目的：为了弥补传统检测方法在检测效果上的缺陷，实现连续地从磁场平面获得其均匀度的数据。方法：设计了一个运动探测器来进行磁场的均匀性检测，将摄取的信号经过转换和数据处理，最后通过计算机仿真对基于有限测量点的传统方法进行了比较。结果：传统检测法的结果与检测时的采样方式（采点数和采点位置）密切相关。在仿真环境中同样的磁场在不同的检测方式下很大可能会得到多个不同的且不具有近似性的结果，特别是在不均匀性不规则分布的磁场中：而本设计只得到唯一的检测结果，并且可以看到检测视野内采点数越多其检测结果将越逼近本设计的结果。结论：本设计能有效弥补传统检测方法充分度和精确度不足的缺陷，同时也说明磁场的均匀性检测应该从连续平面获取数据。     

Feeding behaviors during home‐based treatment of moderate acute malnutrition using corn‐soy blends or lipid‐based nutrient supplements

Feeding behaviors have an important impact on children's nutritional status and are essential to consider when implementing nutrition programs. The objective of this study was to explore and compare feeding behaviors related to supplementary feeding with corn‐soy blends (CSB) and lipid‐based nutrient supplements (LNS) based on best practice feeding behaviors. The study was conducted as part of a randomized controlled trial assessing the effectiveness of new formulations of CSB and LNS and comprised 1,546 children from 6 to 23 months. The study included a mixed methods approach using questionnaires, focus group discussions and home visits and interviews with a subsample of 20 caretakers of trial participants. We found that LNS, compared to CSB, were more likely to be mixed into other foods (OR [95% CI] 1.7 [1.3–2.2], p = <.001), served with a meal (OR [95% CI] 1.6 [1.1–2.3], p = <.018)or between meals (OR [95% CI] 1.5 [1.1–1.9], p = <.005), and fed using an encouraging feeding style (mean difference in percentage points [95% CI] 23% [6%:40%], p = .01). CSB were more likely to be fed using a forced feeding style (mean difference in percentage points [95% CI] 18% [3%:33%], p = .02) and were often observed to be served unprepared. The main differences in feeding behaviors between the two diet groups were linked to how and when supplements were served. Educational instructions should therefore be adapted according to the supplement provided; when providing CSB, efforts should be made to promote an encouraging feeding style, and emphasis should be made to ensure preparations are made according to recommendations.