Preparation of honokiol-loaded chitosan microparticles via spray-drying method intended for pulmonary delivery

It has been demonstrated that spray-drying is a powerful method to prepare dry powders for pulmonary delivery. This paper prepared dispersible dry powders based on chitosan and mannitol containing honokiol nanoparticles as model drug. The results showed that the prepared microparticles are almost spherical and have appropriate aerodynamic properties for pulmonary delivery (aerodynamic diameters was between 2.8–3.3 μm and tapped density ranging from 0.14–0.?18?g/cm³). Moreover, surface morphology and aerodynamic properties of the powders were strongly affected by the content of mannitol. Fourier transform infra-red (FTIR) spectrum of powders indicated that the honokiol nanoparticles were successfully incorporated into microparticles. In vitro drug release profile was also observed. The content of mannitol in powders significantly influenced the release rate of honokiol from matrices.     

Sustained delivery of salbutamol and beclometasone from spray-dried double emulsions

The sustained delivery of multiple agents to the lung offers potential benefits to patients. This study explores the preparation of highly respirable dual-loaded spray-dried double emulsions. Spray-dried powders were produced from water-in-oil-in-water (w/o/w) double emulsions, containing salbutamol sulphate and/or beclometasone dipropionate in varying phases. The double emulsions contained the drug release modifier polylactide co-glycolide (PLGA 50 : 50) in the intermediate organic phase of the original micro-emulsion and low molecular weight chitosan (Mw<190 kDa: emulsion stabilizer) and leucine (aerosolization enhancer) in the tertiary aqueous phase. Following spray-drying resultant powders were physically characterized: with in vitro aerosolization performance and drug release investigated using a Multi-Stage Liquid Impinger and modified USP II dissolution apparatus, respectively. Powders generated were of a respirable size exhibiting emitted doses of over 95% and fine particle fractions of up to 60% of the total loaded dose. Sustained drug release profiles were observed during dissolution for powders containing agents in the primary aqueous and secondary organic phases of the original micro-emulsion; the burst release of agents was witnessed from the tertiary aqueous phase. The novel spray-dried emulsions from this study would be expected to deposit and display sustained release character in the lung.     

Theophylline particle design using chitosan by the spray drying

Solid dispersions of theophylline with chitosan as a carrier were prepared using a spray-drying method. Chitosan dissolved in an acid solution forms a gel, but it does not dissolve in an alkaline solution. Therefore, drugs which form composite particles with chitosan would gradually be released in an acid solution, and are expected to have considerably sustained release in an alkaline solution. In this study, we aimed to apply this ability to sustained release pharmaceutics.

In this study, we used theophylline as a model drug and chitosan as a carrier. Mixtures of chitosan and the drug in prescribed ratios were dissolved in an acid solution.

The physicochemical properties of the solid dispersions obtained were investigated by powder X-ray diffraction, differential scanning calorimetry, and dissolution rate analyses, with a view to clarify the effect of crystallinity on the dissolution rate. Furthermore, the interaction between the drug and the carrier was investigated by FT-IR analysis.

The powder X-ray diffraction intensity of the drug in the spray-dried samples decreased with an increase in chitosan contents, which also caused changes from crystalline to amorphous forms. These results indicated that the system formed a solid dispersion. The dissolution profiles of the drug from the physical mixtures and solid dispersions were almost the same at pH 1.2. However, at pH 6.8, the release from the solid dispersions was sustained more than that from the physical mixtures. The FT-IR spectroscopy for the theophylline solid dispersions suggested that the carbonyl group of theophylline and the amino group of chitosan formed a hydrogen bond.

Mass median aerodynamic diameter (MMAD) was measured by using a cascade impactor to evaluate the possibility of solid dispersions as dry powder inhalations. The MMAD of the spray-dried theophylline-chitosan systems were 4.5–5.0 μm. The results suggested that the spray-drying method is usefull to produce dry powders for inhalation.     

Carbomer-modified spray-dried respirable powders for pulmonary delivery of salbutamol sulphate

The present study investigates the feasibility of using two types of carbomer (971 and 974) to prepare inhalable dry powders that exhibit modified drug release properties. Powders were prepared by spray-drying formulations containing salbutamol sulphate, 20-50% w/w carbomer as a drug release modifier and leucine as an aerosolization enhancer. Following physical characterization of the powders, the aerosolization and dissolution properties of the powders were investigated using a Multi-Stage Liquid Impinger and a modified USP II dissolution apparatus, respectively. All carbomer 974-modified powders and the 20% carbomer 971 powder demonstrated high dispersibility, with emitted doses of at least 80% and fine particle fractions of approximately 40%. The release data indicated that all carbomer-modified powders displayed a sustained release profile, with carbomer 971-modified powders obeying first order kinetics, whereas carbomer 974-modified powders obeyed the Higuchi root time kinetic model; increasing the amount of carbomer 971 in the formulation did not extend the duration of drug release, whereas this was observed for the carbomer 974-modified powders. These powders would be anticipated to deposit predominately in the lower regions of the lung following inhalation and then undergo delayed rather than instantaneous drug release, offering the potential to reduce dosing frequency and improve patient compliance.     

Preparation,In Vitro Characterization,and In Vivo Pharmacokinetic Evaluation of Respirable Porous Microparticles Containing Rifampicin

This study aimed to prepare and evaluate rifampicin microparticles for the lung delivery of rifampicin as respirable powder. The microparticles were prepared using chitosan by the spray-drying method and evaluated for aerodynamic properties and pulmonary drug absorption. To control the drug release, tripoly-phosphate in different concentrations 0.6, 0.9, 1.2, and 1.5 was employed to get a sustained drug release profile. The microparticles were evaluated for drug loading, % entrapment efficiency, tapped density, morphological characteristics, and in vitro drug release studies. Aerosol properties were determined using the Andersen cascade impactor. Porous microparticles with particle sizes (d_0.5) less than 10 μm were obtained. The entrapment of rifampicin in microparticles was up to 72%. In vitro drug release suggested that the crosslinked microparticles showed sustained release for more than 12 hrs. The drug release rate was found to be decreased as the TPP concentration was increased. The microparticles showed a fine particle fraction in the range of 55–63% with mass median aerodynamic diameter (MMAD) values below 3 μm. The in vivo pulmonary absorption of the chitosan microparticles suggested a sustained drug release profile up to 72 hrs with an elimination rate of 0.010 per hr. The studies revealed that the spray-dried porous microparticles have suitable properties to be used as respirable powder in rifampicin delivery to the lungs.     

Carbomer-modified spray-dried respirable powders for pulmonary delivery of salbutamol sulphate

Abstract

The present study investigates the feasibility of using two types of carbomer (971 and 974) to prepare inhalable dry powders that exhibit modified drug release properties. Powders were prepared by spray-drying formulations containing salbutamol sulphate, 20–50% w/w carbomer as a drug release modifier and leucine as an aerosolization enhancer. Following physical characterization of the powders, the aerosolization and dissolution properties of the powders were investigated using a Multi-Stage Liquid Impinger and a modified USP II dissolution apparatus, respectively. All carbomer 974-modified powders and the 20% carbomer 971 powder demonstrated high dispersibility, with emitted doses of at least 80% and fine particle fractions of ～40%. The release data indicated that all carbomer-modified powders displayed a sustained release profile, with carbomer 971-modified powders obeying first order kinetics, whereas carbomer 974-modified powders obeyed the Higuchi root time kinetic model; increasing the amount of carbomer 971 in the formulation did not extend the duration of drug release, whereas this was observed for the carbomer 974-modified powders. These powders would be anticipated to deposit predominately in the lower regions of the lung following inhalation and then undergo delayed rather than instantaneous drug release, offering the potential to reduce dosing frequency and improve patient compliance.     

Formulation and in vitro evaluation of highly dispersive insulin dry powder formulations for lung administration

The aim of this work was to develop highly dispersible and dry formulations of insulin for use in dry powder inhalers (DPIs) using high-pressure homogenisation (HPH) and spray-drying. Several formulations were evaluated, including formulations spray-dried without excipients and formulations coated with lipids. A physiological lipid composition based on a mixture of cholesterol and phospholipids was used to form the coating film around micronised drug particles. The production technique and excipients were chosen in order to limit the degradation of the active ingredient.The resulting powders exhibited a size and shape suitable for the deep lung deposition of drugs, and good aerodynamic features were obtained for the different formulations tested, with fine particle fractions between 46% and 63% vs. 11% for raw insulin powder. The presence of a lipid coating of up to 30% (w/w) did not significantly affect the aerodynamic behaviour, and the coated formulations also exhibited a decreased residual moisture content of between 2.3% and 3.7% vs. 4.8% for raw insulin, which should improve the long-term stability of the protein formulations. No degradation of the insulin molecule occurred during the HPH/spray-drying process, as it was shown using an HPLC method (insulin content between 98.4% and 100.5%), and the content in high molecular weight proteins, assessed using a gel filtration method, stayed below 0.4%.     

硫酸特布他林干粉吸入剂制备工艺的优化研究

目的:优化硫酸特布他林干粉吸入剂的制备工艺。方法:采用喷雾干燥技术制备硫酸特布他林干粉吸入剂,采用双层液体碰撞器测定其体外肺沉积率,扫描电镜观察干粉的表观形貌,热重分析仪测定干粉的水分含量,激光粒度测定仪测定粒径大小,以产品收率、水分含量、粉末的空气动力学粒径及体外肺沉积率为考察指标,通过正交设计结合多指标综合评价法优化最佳制备工艺。结果:通过正交试验-多指标综合评价,最佳制备工艺为:喷雾压力190 kPa,干燥风速0.7 m3.min-1,供液速度7.0 mL.min-1,入口温度120℃。结论:按最佳制备工艺制得的干粉收率为50.54%,水分含量为0.467%,空气动力学粒径为1.80μm,体外肺沉积率为55.19%。正交试验结合多指标综合评价法用于硫酸特布他林干粉吸入剂制备工艺的优化有效可用。     

Chitosan microspheres with hydrocortisone and hydrocortisone–hydroxypropyl-β-cyclodextrin inclusion complex

In the present study, an inclusion complex composed of hydrocortisone acetate (HC) and hydroxypropyl-β-cyclodextrin (HPβCD) was prepared by the spray-drying method. HC alone, HC inclusion complex or HC with HPβCD as a physical mixture were incorporated into chitosan microspheres by spray-drying. The inclusion complex and microspheres were characterized by X-ray powder diffractometry and differential scanning calorimetry (DSC). Microspheres were studied with respect to particle size distribution, drug content and in vitro drug release. The results indicate that the HCHPβCD inclusion complex is more water soluble than HC alone. The HC release rates from chitosan microspheres were influenced by the drug/polymer ratio in the manner that an increase in the release rate was observed when the drug loading was decreased. However, release data from all samples showed significant improvement of the dissolution rate for HC, with 25–40% of the drug being released in the first hour compared with about 5% for pure HC. The complexation method and microsphere preparation method (spray-drying) is simple with great potential for industrial production.     

Spray-dried carbamazepine-loaded chitosan and HPMC microspheres: preparation and characterisation

In this study, the potential of the spray-drying technique for preparing microspheres able to modify the release profile of carbamazepine was investigated. Low-, medium- and high-molecular-weight chitosan and hydroxypropyl methylcellulose (HPMC) in different drug-polymer ratios were used for the preparation of microspheres. The microspheres, characterized by X-ray powder diffractometry (XRD) and differential scanning calorimetry (DSC), were also studied with respect to particle size distribution, drug content and drug release. The results indicated that the entrapment efficiency (EE), as well as carbamazepine release profile, depended on polymeric composition and drug-polymer ratios of the microspheres prepared. The best entrapment efficiencies were obtained when chitosan of low-molecular-weight (CL) or HPMC were used for the microencapsulation. For all types of polymer used, the microspheres with low carbamazepine loading (6.3% w/w) showed better control of drug release than the microspheres with higher drug loadings. The HPMC microspheres showed the slowest carbamazepine release profile with no initial burst effect. Carbamazepine release profiles from ternary systems, carbamazepine-CL-HPMC microspheres, depended mostly on HPMC content and showed similar carbamazepine release profile as CL microspheres when HPMC content was low (9:1 CL-HPMC ratio, w/w). Otherwise, the carbamazepine release from CL-HPMC microspheres was remarkably faster than from either chitosan or HPMC microspheres. The release profile of carbamazepine from the microspheres was highly correlated with the crystalline changes occurring in the matrix.     

Hydrogels based on interpenetrating network of chitosan and polyvinyl pyrrolidone for pH-sensitive delivery of repaglinide

The aim of this study was to develop a pH-sensitive chitosan/polyvinyl pyrrolidone (PVP) based controlled drug release system for repaglinide. The hydrogels were synthesised by crosslinking chitosan and PVP blend with glutaraldehyde to form a semi-interpenetrating polymer network (semi-IPN). These semi-IPNs were studied for their content uniformity, swelling index (SI), mucoadhesion, wettability, in vitro release and their release kinetics. The hydrogels showed more than 95% loading of repaglinide. These hydrogels showed high swelling and mucoadhesion under acidic conditions. The swelling was found due to the protonation of a primary amino group on chitosan. In acidic condition chitosan was ionized, and adhesion occurred between the positively charged chitosan and the negatively charged mucus. In the physiological condition less swelling was noticed. In vitro release study revealed that formulation containing chitosan (2% w/v) and PVP (4% w/v) in the ratio of 14:6 w/w showed complete drug release after 12h. Release profile showed that all the formulations followed non-fickian diffusion mechanism (diffusion coupled with swelling). Fourier transform infrared (FTIR) spectroscopic analysis revealed proper crosslinking of polymer and formation of semi-IPN as well as presence of drug in the formulation. Differential scanning calorimetry (DSC) and powder x-ray diffraction (p-XRD) study revealed the presence of repaglinide in crystalline form in the formulations. The surface morphology of semi-IPN was studied before and after dissolution in simulated gastric fluid (SGF, pH 1.2) which indicated generation of open channel-like structure in hydrogel after dissolution. The results of study suggest that semi-IPNs of chitosan/PVP are potent candidates for delivery of repaglinide in acidic environment.     

Effect of manufacturing parameters on the characteristics of vitamin C encapsulated tripolyphosphate-chitosan microspheres prepared by spray-drying

To prepare the sustained release vitamin C carriers, vitamin C was successfully encapsulated in tripolyphosphate (TPP) cross-linked chitosan (TPP-chitosan) microspheres by the spray-drying method at different manufacturing conditions. Manufacturing parameters (inlet temperature, liquid flow rate, chitosan concentration and volume of 1% w/v TPP solution) had a significant influence on the characteristics of thus prepared microspheres. The optimum spray-drying conditions such as inlet temperature, liquid flow rate and compressed air flow rate for the encapsulation of vitamin C in TPP-chitosan microspheres was found to be 170 degrees C, 2 ml min(-1) and 101 min(-1), respectively. The size and yield of the TPP-chitosan microspheres ranged from 3.9-7.3 microm and 54.5-67.5%, respectively. The encapsulation efficiency of TPP-chitosan microspheres ranged from 45.72-68.7% and it decreased with the increasing volume of 1% w/v TPP solution. At the same cross-linking extent, the encapsulation efficiency of TPP-chitosan microspheres increased when the concentration of chitosan was increased from 0.5-1% w/v. Effect of volume of 1% w/v TPP solution on the surface morphology of chitosan microspheres was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). These studies revealed that chitosan solution (250 ml) cross-linked with 15 ml 1% w/v TPP solution produced more porous microspheres than that cross-linked with 5 and 10 ml TPP solution. The release rate of vitamin C from TPP-chitosan microspheres decreased when the concentration of chitosan was increased from 0.5-1.0% w/v. Vitamin C release rate was also modulated by varying the volume of 1% w/v TPP solution. The release rate of vitamin C from TPP-chitosan microspheres decreased with increasing volume (5-15 ml) of 1% w/v TPP solution.     

Characteristics of vitamin C encapsulated tripolyphosphate-chitosan microspheres as affected by chitosan molecular weight

In this paper, the effect of chitosan molecular weight on the characteristics (size, encapsulation efficiency, zeta potential, surface morphology and release rate) of vitamin C encapsulated tripolyphosphate cross-linked chitosan (TPP-chitosan) microspheres. The molecular weight of chitosan had a noticeable influence on the size, encapsulation efficiency, zeta potential, surface morphology and controlled release behaviour of the vitamin C encapsulated TPP-chitosan microspheres. The mean particle size and encapsulation efficiencies of TPP-chitosan microspheres were 3.1, 4.9 and 6.7 microm and 67.25, 60.43 and 52.74% for the microspheres prepared using low, medium and high molecular weight chitosan, respectively. All the TPP-chitosan microspheres (low, medium and high molecular weight) had positive charge on their surface. The zeta potential of the TPP-chitosan microspheres prepared using low, medium and high molecular weight chitosan was 41.25, 40.84 and 39.13 mV, respectively. The particle sizes of TPP-chitosan microspheres increased with increases in chitosan molecular weight. Molecular weight of chitosan did not affect significantly the % yield of TPP-chitosan microspheres prepared by spray-drying. The influence of chitosan molecular weight on the surface morphology of vitamin C encapsulated TPP-chitosan microspheres was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). It was observed that, as the molecular weight of chitosan increases, TPP-chitosan microspheres with uniform spherical shape could be obtained. The physical state of vitamin C (amorphous or crystalline) in TPP-chitosan matrix was studied by X-ray diffraction (XRD) and it was found that vitamin C is dispersed at the molecular level (amorphous) in the TPP-chitosan matrix. Release rate of the vitamin C from TPP-chitosan microspheres was significantly affected by the chitosan molecular weight. The release rate decreased with increase in the chitosan molecular weight. The release of vitamin C from TPP-chitosan microspheres followed Fick's law of diffusion.     

Characterisation of salmon calcitonin in spray-dried powder for inhalation. Effect of chitosan

Salmon calcitonin (sCT) powders suitable for inhalation, containing chitosan and mannitol as absorption enhancer and protection agent, respectively, were prepared using a spray-drying process. The effect of chitosan on physicochemical stability of sCT in the dry powder was investigated by different analytical techniques. High-performance liquid chromatography (HPLC) analysis indicated that sCT was chemically stable upon spray-drying. With the proportion of chitosan in spray-drying formulation being increased, dissolution of sCT from the dry powders was decreased both in phosphate buffer and acetate buffer. The thioflavine T fluorescence assay showed that no fibrils were present in the spray-dried powder. However, sCT partly fibrillated in the phosphate buffer, but not in acetate buffer. Fourier transform infrared (FTIR) spectra showed that the secondary structure of sCT was slightly changed in the dry powder, yet no aggregate signal was observed. Circular dichroism analysis indicated that the structure of sCT in an aqueous formulation was slightly altered by addition of chitosan. Nevertheless, recovery of sCT was not influenced by chitosan in the aqueous formulation as indicated by HPLC analysis. This study suggested that sCT, in absence of any additives, was stable during the spray-drying process under certain conditions. Addition of chitosan affects recovery of sCT from spray-dried powders, which may be due to formation of a partially irreversible complex between the protein and chitosan during the spray-drying process.     

Chitosan salts as nasal sustained delivery systems for peptidic drugs

The aim of this study was to describe a sustained drug release system based on chitosan salts for vancomycin hydrochloride delivery. Chitosan lactate, chitosan aspartate, chitosan glutamate and chitosan hydrochloride were prepared by spray-drying technique. Vancomycin hydrochloride was used as a model peptidic drug, the nasal sustained release of which should avoid first-pass metabolism in the liver. This in-vitro study evaluated the influence of chitosan salts on the release behaviour of vancomycin hydrochloride from the physical mixtures at pH 5.5 and 7.4. In-vitro release of vancomycin was retarded by chitosan salts and, in particular, chitosan hydrochloride provided the lowest release of vancomycin.     

Characteristics of vitamin C encapsulated tripolyphosphate-chitosan microspheres as affected by chitosan molecular weight

In this paper, the effect of chitosan molecular weight on the characteristics (size, encapsulation efficiency, zeta potential, surface morphology and release rate) of vitamin C encapsulated tripolyphosphate cross-linked chitosan (TPP-chitosan) microspheres. The molecular weight of chitosan had a noticeable influence on the size, encapsulation efficiency, zeta potential, surface morphology and controlled release behaviour of the vitamin C encapsulated TPP-chitosan microspheres. The mean particle size and encapsulation efficiencies of TPP-chitosan microspheres were 3.1, 4.9 and 6.7?µm and 67.25, 60.43 and 52.74% for the microspheres prepared using low, medium and high molecular weight chitosan, respectively. All the TPP-chitosan microspheres (low, medium and high molecular weight) had positive charge on their surface. The zeta potential of the TPP-chitosan microspheres prepared using low, medium and high molecular weight chitosan was 41.25, 40.84 and 39.13?mV, respectively. The particle sizes of TPP-chitosan microspheres increased with increases in chitosan molecular weight. Molecular weight of chitosan did not affect significantly the % yield of TPP-chitosan microspheres prepared by spray-drying. The influence of chitosan molecular weight on the surface morphology of vitamin C encapsulated TPP-chitosan microspheres was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). It was observed that, as the molecular weight of chitosan increases, TPP-chitosan microspheres with uniform spherical shape could be obtained. The physical state of vitamin C (amorphous or crystalline) in TPP-chitosan matrix was studied by X-ray diffraction (XRD) and it was found that vitamin C is dispersed at the molecular level (amorphous) in the TPP-chitosan matrix. Release rate of the vitamin C from TPP-chitosan microspheres was significantly affected by the chitosan molecular weight. The release rate decreased with increase in the chitosan molecular weight. The release of vitamin C from TPP-chitosan microspheres followed Fick's law of diffusion.     

Swellable microparticles as carriers for sustained pulmonary drug delivery

In this investigation, novel biodegradable physically crosslinked hydrogel microparticles were developed and evaluated in vitro as potential carriers for sustained pulmonary drug delivery. To facilitate sustained release in the lungs, aerosols must first navigate past efficient aerodynamic filtering to penetrate to the deep lung (requires small particle size) where they must then avoid rapid macrophage clearance (enhanced by large particle size). The strategy suggested in this study to solve this problem is to deliver drug‐loaded hydrogel microparticles with aerodynamic characteristics allowing them to be respirable when dry but attain large swollen sizes once deposited on moist lung surfaces to reduce macrophage uptake rates. The microparticles are based on PEG graft copolymerized onto chitosan in combination with Pluronic® F‐108 and were prepared via cryomilling. The synthesized polymers used in preparation of the microparticles were characterized using FTIR, EA, 2D‐XRD, and differential scanning calorimetry (DSC). The microparticles size, morphology, moisture content, and biodegradation rates were investigated. Swelling studies and in vitro drug release profiles were determined. An aerosolization study was conducted and macrophage uptake rates were evaluated against controls. The microparticles showed a respirable fraction of approximately 15% when prepared as dry powders. Enzymatic degradation of microparticles started within the first hour and about 7–41% weights were remaining after 240 h. Microparticles showed sustained release up to 10 and 20 days in the presence and absence of lysozyme, respectively. Preliminary macrophage interaction studies indicate that the developed hydrogel microparticles significantly delayed phagocytosis and may have the potential for sustained drug delivery to the lung. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2343–2356, 2010     

盐酸氨溴索干粉吸入剂的制备工艺

目的优化盐酸氨溴索干粉吸入剂的制备工艺。方法采用喷雾干燥法制备盐酸氨溴索干粉吸入剂,采用双层液体碰撞器测定盐酸氨溴索干粉吸入剂体外沉积率,扫描电镜观察粉粒的形态,激光粒度测定仪测定粒径大小,以产品收率、粉末的空气动力学径、休止角及体外沉积率为考察指标,通过正交设计结合多指标综合评价法优化最佳制备工艺。结果通过正交试验-多指标综合评价,最佳制备工艺为:进口温度110℃、喷液速度1.8 mL.min-1、泵压170 kPa、气流量0.7 m3.min-1。结论按最佳制备工艺制得的干粉收率的质量分数为62.10%,空气动力学径Da 3.05μm,休止角36.16°,沉积率32.05%。正交实验结合多指标综合评价法用于盐酸氨溴索干粉吸入剂制备工艺的优化实用有效。     

交联甲壳胺-PEG-尼莫地平缓释颗粒性质及释药特性

目的研究交联甲壳胺PEG尼莫地平(rosslinked chitosan PEG nimodipine,RCPN)缓释颗粒的性质及体外释药特性。方法采用乳化交联法制备交联甲壳胺PEG尼莫地平缓释颗粒;用红外光谱(IR)对其结构进行表征;扫描电子显微镜(SEM)观察颗粒形态及表面结构;考察颗粒的粒径分布、颗粒中药物含量测定及在不同介质中药物的释放。结果电镜扫描显示颗粒呈球形,表面圆整,个别表面有凹凸状;RCPN缓释颗粒平均粒径为1.20 mm;红外图谱显示甲壳胺的氨基和戊二醛的羰基发生反应生成Schiffs碱。该颗粒剂有缓释作用,释药特性符合Higuchi方程。结论以交联甲壳胺做为辅料制备的缓释颗粒在体外具有缓释作用。     

Dry powder inhalations containing thymopentin and its immunomodulating effects in Wistar rats

Thymopentin (TP5), a synthetic pentapeptide, has been used in clinic as a modulator for immunodeficiences through intramuscular administration. The purpose of this study was to design and evaluate dry powder inhalations (DPIs) for pulmonary delivery of TP5. Dry powder inhalations containing leucine (a dispersibility enhancer), mannitol, and lactose (bulking agents) were prepared by spray-drying from aqueous formulations. The formulation components on the aerosolisation characteristics of spray-dried powders were investigated through the use of various amount of leucine, lactose and mannitol. Following spray-drying, resultant powders were characterized using scanning electron microscopy, laser diffraction and tapped density measurements, and the aerosolisation performance was determined using Twin Stage Impinger. The immunosuppression Wistar rats model was constructed to evaluate the immunomodulating effects of TP5 DPIs in vivo. The results of T-lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+ ratio) analyses suggest that TP5 DPIs have modulating effects. On an overall evaluation, TP5 pulmonary delivery DPIs may be feasible for the future clinical application.