Design of prolonged-release microcapsules containing diclofenac sodium for oral suspensions and their preparation by the Wurster process

Prolonged-release microcapsules of diclofenac sodium (DS), an acidic drug, applicable as an oral suspension for twice-a-day administration were designed. The microcapsules with a mass median diameter of around 100 μm and a high drug content were intended to exhibit a preferably prolonged release of highly water-soluble DS when prepared by the Wurster process–a spray coating method using a spouted bed assisted with a draft tube. The microcapsule was composed of a calcium carbonate core of 32–44 μm, a drug-layer of DS, hydroxypropyl cellulose and polyethyleneglycol 6000, an undercoat of Eudragit L30D and a release-sustaining coat of Eudragit RS30D. Eudragit L30D films were undercoated to decrease the solubility of DS within the environment of the microcapsules and thereby to prolong the drug release. This made it possible to decrease the amount of Eudragit RS30D membrane required to prolong the drug release, leading to decrease in the particle size of products and achievement of high drug content. As a result, prolonged release microcapsules with a mass median diameter of 92 μm and a drug content of 29% could be obtained.     

Dissolution stability studies of suspensions of prolonged-release diclofenac microcapsules prepared by the Wurster process: I. Eudragit-based formulation and possible drug-excipient interaction

The aim was to evaluate possible interaction in solid and liquid state of the drug with formulation excipients consequent to very fast drug release of diclofenac-Eudragit prolonged release microcapsules. The microcapsules were prepared by drug layering on calcium carbonate cores and coated with Eudragit RS 30D and L30D-55 as previously reported. Suspension of the microcapsules was prepared using microcrystalline cellulose/sodium carboxymethyl cellulose (Avicel CL-611) as medium. In vitro dissolution testing of the suspension was done, and, based on the dissolution results, possible interaction between diclofenac and Eudragit and Avicel in the medium was studied. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analyses were performed using 1:1 binary, 1:1:1 ternary mixtures and a ratio equivalent to that in the formulation. The mixtures were prepared by mixing the dispersions--Eudragit RS 30D or L30D-55 with the drug or other components, followed by drying at 60 degrees C for 48 h. Dry mixing was done using the powder equivalents of the polymers, Eudragit RS PO and L100-55, Avicel and calcium carbonate. In vitro dissolution of the suspended microcapsules showed a very fast release after 48 h (T50 = <1 h) compared to the solid microcapsules (T50 = 6 h). DSC curves of the formulation components or microcapsules did not show the characteristic endothermic peak of diclofenac at 287 degrees C. Powder X-ray diffraction of the binary or ternary mixtures of diclofenac and Eudragit polymers indicated reduction, shift or modification of the crystalline peaks of the drug or excipients at 2theta of 12 degrees and 18 degrees , suggestive of interaction. Some changes in drug peak characteristics at 18 degrees and 23 degrees were observed for Avicel/drug mixture, though not significant. The DSC curves of the binary mixture of diclofenac co-dried with liquid forms of Eudragit (i.e. RS 30D or L30D-55) revealed greater interaction compared to the curves of drug and powdered forms of Eudragit (RS PO or L100-55). This was depicted by greater shift in fusion points of the mixtures relative to the drug. However, comparing the RS and L-type Eudragit, the latter generally showed greater interaction with the drug. Interaction between diclofenac and L-type Eudragit polymers can occur in liquid formulations.     

Dissolution stability studies of suspensions of prolonged-release diclofenac microcapsules prepared by the Wurster process: I. Eudragit-based formulation and possible drug-excipient interaction

The aim was to evaluate possible interaction in solid and liquid state of the drug with formulation excipients consequent to very fast drug release of diclofenac-Eudragit® prolonged release microcapsules. The microcapsules were prepared by drug layering on calcium carbonate cores and coated with Eudragit® RS 30D and L30D-55 as previously reported. Suspension of the microcapsules was prepared using microcrystalline cellulose/sodium carboxymethyl cellulose (Avicel® CL-611) as medium. In vitro dissolution testing of the suspension was done, and, based on the dissolution results, possible interaction between diclofenac and Eudragit and Avicel in the medium was studied. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analyses were performed using 1:1 binary, 1:1:1 ternary mixtures and a ratio equivalent to that in the formulation. The mixtures were prepared by mixing the dispersions—Eudragit RS 30D or L30D-55 with the drug or other components, followed by drying at 60°C for 48?h. Dry mixing was done using the powder equivalents of the polymers, Eudragit RS PO and L100-55, Avicel and calcium carbonate. In vitro dissolution of the suspended microcapsules showed a very fast release after 48?h (T₅₀?=?<1?h) compared to the solid microcapsules (T₅₀?=?6?h). DSC curves of the formulation components or microcapsules did not show the characteristic endothermic peak of diclofenac at 287°C. Powder X-ray diffraction of the binary or ternary mixtures of diclofenac and Eudragit polymers indicated reduction, shift or modification of the crystalline peaks of the drug or excipients at 2θ of 12° and 18°, suggestive of interaction. Some changes in drug peak characteristics at 18° and 23° were observed for Avicel/drug mixture, though not significant. The DSC curves of the binary mixture of diclofenac co-dried with liquid forms of Eudragit (i.e. RS 30D or L30D-55) revealed greater interaction compared to the curves of drug and powdered forms of Eudragit (RS PO or L100-55). This was depicted by greater shift in fusion points of the mixtures relative to the drug. However, comparing the RS and L-type Eudragit, the latter generally showed greater interaction with the drug. Interaction between diclofenac and L-type Eudragit polymers can occur in liquid formulations.     

Binding of drugs to ion-exchange resins in simulated gastric fluid

The binding of 13 frequently abused drugs to two ion-exchange resins was studied in simulated gastric fluid. The results were compared with those previously obtained with activated charcoal as the adsorbent. The ion-exchange resins adsorbed the drugs more slowly than activated charcoal, and the binding capacities of the resins were inferior. These ion-exchange resins are unlikely to be very useful in removing drugs from the stomach.     

优化地塞米松类脂纳米粒的制备工艺

目的筛选地塞米松类脂纳米粒(DSLN)的制备工艺。方法根据文献和单因素实验初选DSLN的制备工艺,按球面对称设计表设计实验,优化制备工艺并进行结果预测及验证。结果投药量为60 mg,三硬脂酸甘油酯用量110 mg,F68浓度2%。按优化条件制备的DSLN的体积径为198 nm,载药量为9%。结论按照球面对称设计优选的条件制备DSLN,其目标值在预测值范围内。     

A novel approach to prepare insulin-loaded poly(lactic-co-glycolic acid) microcapsules and the protein stability study

The purpose of this study was to propose a new preparation method to fabricate insulin-loaded poly(lactic-coglycolic acid) (PLGA) microparticles satisfying protein loading, release profiles, burst release, and particularly stability of the encapsulated protein. Insulin-loaded microcapsules were produced by a single phase o/o solvent evaporation method. The characteristics of the microcapsules were determined by various methods: the surface morphology and size of microparticles by atomic force microscopy and scanning electron microscopy, insulin crystalinity and drug-polymer interactions by XRD, DSC, and FTIR, chemical integrity and aggregation of insulin using HPLC and SDS-PAGE, the protein secondary structure by far ultraviolet-circular dichroism (CD), the antigenicity activity of insulin with ELISA techniques. PLGA microparticles showed smooth surfaces with microcapsule. Encapsulation efficiency of 51% and constant insulin release rate with initial insulin burst release of 24% was obtained. Encapsulated and released insulin was in the intact form and it was dispersed in crystalline state in the polymer matrix. Ease of manufacturing under mild preparation conditions, high level of drug entrapment, desirable release pattern with relatively low initial burst effect and an ability to preserve protein structure are the advantages which are offered by the developed protein encapsulation method.     

喷雾干燥法制备诺西肽掩味微囊的研究

目的探索喷雾干燥法制备诺西肽微囊的最佳掩味工艺。方法以干粉得率、包封率、掩味效果、吸湿性作为指标,采用正交设计法确定最佳喷雾干燥工艺参数。结果最佳工艺参数为：进风温度185℃,进料速度600mL.h-1,压缩空气压力0.5 mPa。结论该工艺合理,诺西肽微囊质量达到预期要求,产品稳定性好,为工业化生产提供了实验依据。     

Preparation of microcapsules for skin allergy testing by the solvent evaporation process

Polyurethanes and polyvinyl alcohol modified by stearyl isocyanate are used as a matrix for microparticles made by a solvent evaporation process to encapsulate allergenic molecules, with petrolatum used as a neutral vehicle. The encapsulation yields, depending on the agent to be encapsulated, vary from 22 to 45%.