Effect of soluble filler on drug release from stearic acid based compacts

Fatty acids are potentially suitable carriers for use in the design of drug delivery systems, being biocompatible, biodegradable, of low toxicity inexpensive, with drug release being approximately proportional to the square root of time. However, at low drug loadings, below the critical percolation threshold, release is likely to be extremely slow and incomplete. To overcome these problems, we have investigated the use of increasing amounts of the soluble filler lactose on drug release. Benzoic acid and insulin were used as model low and high molecular weight drugs, respectively. At a 10% loading, benzoic acid was an order of magnitude higher than that observed for insulin. Using lactose as soluble filler, it was possible to effect greater release with increasing lactose content in the range 10-50%. Values of F, the formation factor, increased, but not to the same extent as for increased drug loading. The Higuchi release rate constant, k, was similar at lactose loadings of 5-20%, but increased rapidly at higher lactose loadings. Quantitatively, the addition of lactose yielded release rate constants 1.2-3.6 times greater than the value for lactose-free compacts in the case of benzoic acid and two- to five-fold in the case of insulin. A linear relationship was demonstrated between k, and the percentage soluble fraction of the matrix above the percolation threshold.     

Polymer particle erosion controlling drug release. I. Factors influencing drug release and characterization of the release mechanism

The present study deals with controlled drug delivery from hydrocolloid tablets by polymer particle erosion. The influence of excipients and formulation factors on the dissolution behaviour of the methyl hydroxyethyl cellulose (MHEC)-tablets is investigated. Linear drug release with low susceptibility to hydrodynamic stress is obtained. The use of drugs with higher solubility leads to a slight acceleration of the release due to the contribution of diffusion to the release process. Higher drug loading and consequently lower polymer content expedites dissolution as well as changes in the tablets' geometry resulting in enlarged release surfaces. Furthermore, alterations of the composition of the dissolution medium affect drug release. However, neither viscosity grade nor the particle size of the polymer or compaction pressure has a marked impact on the dissolution. Investigations to clarify the mechanism of polymer particle erosion include erosion studies and the comparison of different batches of MHEC, of products from different manufacturers and of fibrous trial products. There is evidence that the insoluble fibres within the water soluble MHEC are responsible for the occurrence of polymer particle erosion by disturbing swelling and formation of a thick coherent gel layer and thus, causing erosion of the hydrocolloid tablet with synchronous drug release.     

An investigation into the release of cefuroxime axetil from taste-masked stearic acid microspheres. II. The effects of buffer composition on drug release

The influence of buffer composition on the release of cefuroxime axetil from stearic acid microspheres has been investigated, with particular emphasis on establishing the relationship between buffer composition and release at a single pH value. Studies of drug dissolution and release from spheres in pH 7.0 citrate phosphate buffer (CPB), boric acid buffer (BAB), phosphate buffer mixed (PBM) and Sorensens modified phosphate buffer (SMPB) indicated marked differences in release profile from the spheres, with an approximate rank order of SMPB > CPB approximately BAB > PBM. The role of added sodium was then investigated by examining the release profiles in SMPB and PBM to which sodium ions had been added. Increases in the sodium content from approximately 0.11 to 0.2 M were found to decrease the release rate for the SMPB, while increases from 0.007 to 1.0 M sodium in PBM resulted in a maximum release being seen for the systems containing 0.05 M sodium. Studies on surface disintegration, using scanning electron microscopy (SEM) and sodium uptake using flame emission spectroscopy, indicated an interrelationship between medium composition, disintegration and release. The data are discussed in terms of the possible mechanisms associated with drug release from these spheres.     

Enhancement of griseofulvin release from liquisolid compacts

The potential of hydrophilic aerogel formulations and liquisolid systems to improve the release of poorly soluble drugs was investigated using griseofulvin as model drug. The in vitro release rates of this drug formulated as directly compressed tablets containing crystalline griseofulvin were compared to aerogel tablets with the drug adsorbed onto hydrophilic silica aerogel and to liquisolid compacts containing the drug dissolved or suspended in PEG 300. Furthermore, the commonly used carrier and coating materials in liquisolid systems Avicel® and Aerosil® were replaced by Neusilin®, an amorphous magnesium aluminometasilicate with an extremely high specific surface area of 339 m²/g to improve the liquisolid approach.Both the liquisolid compacts containing the drug dissolved in PEG 300 and the aerogel tablets showed a considerably faster drug release than the directly compressed tablets. With liquisolid compacts containing the drug suspended in PEG 300, the release rate increased with rising fraction of dissolved drug in the liquid portion. It could be shown that Neusilin® with its sevenfold higher liquid adsorption capacity than the commonly used Avicel® and Aerosil® allows the production of liquisolid formulations with lower tablet weights.     

Factors influencing liberation of drug from semisolid dosage forms

Liberation of salicylic acid--as a model active agent--was investigated from white petrolatum, creams w/o and o/w types and hydrogels. Active agent was applied in suspended, dissolved forms, in inclusion complexes and solubilized state. The process of liberation was studied by a continuous through-flow method, with Hanson vertical diffusion cell. The results of experiments were evaluated by factorial design method. Increase of the concentration of salicylic acid, polarity of vehicle and solubilized state of drug increased the drug release. It was established that the partitioning released drug was the most important step of drug release. Factors changing partitioning influenced the liberation to the highest degree.     

阿奇霉素缓释微丸体外释药影响因素考察

考察影响阿奇霉素缓释微丸体外释药的各种因素,为阿奇霉素缓释制剂的研制提供实验依据。方法选用微晶纤维素为空白丸芯,将阿奇霉素制成缓释微丸,通过测定体外释放度,考察EC粘度及增重、致孔剂用量、释放介质pH值对阿奇霉素缓释微丸体外释药速率的影响。结果 EC粘度、包衣增重、致孔剂用量、释放介质pH值对释药速率有显著影响。结论选用适宜包衣材料及致孔剂,调节包衣增重,可制备具有理想释药行为的阿奇霉素缓释微丸。     

影响药物鼻黏膜吸收的因素

近年来药物的鼻黏膜吸收受到越来越多的关注,但影响因素却比较复杂。鼻腔的生理因素、黏附聚合物因素和环境因素都会影响鼻腔的黏膜黏附。现综述影响药物鼻黏膜吸收的因素。     

An investigation into the factors influencing drug release from hydrophilic matrix tablets based on novel carbomer polymers

Drug release from hydrophilic matrix tablets can be strongly influenced by the proportion of matrix forming polymer and the dimensions and geometry of the tablets. A complete two-factor, three-level factorial design, followed by multiple regression analysis and response surface methodology, was applied to investigate the influence of polymer level and tablet size on drug release kinetics from hydrophilic matrix tablets prepared with Carbopol 971P and Carbopol 71G. Tablet diameter, radius-to-height ratio, tablet surface area, and surface-area-to-volume ratio were evaluated as independent variables in terms of their applicability to characterize tablet size and geometry. The results indicate that it may be possible to control the rate of drug release by modifying the proportion of carbomer in tablets and tablet dimensions. The practical benefit of these simulations is to optimize the geometry and dimensions of a controlled release device and reduce the number of experiments involved in the development of new controlled release dosage forms.     

Possibility of influencing drug release from polymers--using the example of bead polymers

By the example of the model drug phenobarbital, the authors report of the possibilities of influencing the liberation of drugs from acrylate-based bead polymers. The drug-containing bead polymers produced were studied in vitro (half-change method, beaker device according to Moldenhauer, artificial digestive juices according to Münzel, without addition of enzymes). The composition of a unit-dose preparation, composed of several batches prepared under different conditions, is dealt with. The release values obtained largely meet the requirements made on depot preparations.     

Factors influencing cryoprotective activity and drug leakage from liposomes after freezing

The effects of freezing and thawing conditions and cryoprotective additives on release of streptomycin from lecithin liposomes following freeze-thaw cycles have been investigated. Drug retention was maximized by slow cooling (approx. 1 degree C min-1). At temperatures between 0 degree and -20 degrees C, the extent of drug loss was time-dependent indicating incomplete freezing; below -45 degrees C this effect was abolished and the system was stable. Osmotic gradients across the liposome membrane during freezing were found to have little effect on drug loss. Marked cryoprotective activity was shown by dimethylsulphoxide, glycerol, alanine and glycinebetaine at concentrations of 3% w/v or less. At this concentration sucrose and mannitol had little activity.     

双氯芬酸钠泊洛沙姆凝胶体外释放的影响因素研究

目的:以双氯芬酸钠为模型药,研究泊洛沙姆407(P407)制剂体外释放的影响因素。方法:采用无膜释放法考察不同P407浓度、振荡频率、温度、等渗调节剂、附加剂等对凝胶溶蚀和药物释放的影响。结果:随振荡频率的增加及等渗调节剂PBS,NaC l或葡萄糖的添加,凝胶溶蚀和药物释放增加;P407浓度增加及处方中加入羟甲基纤维素钠(CMC-Na)、羟丙甲纤维素(HPMC)、甲基纤维素(MC)、羧甲基壳聚糖(O-CMC)等抑制了凝胶溶蚀和药物释放;温度升高药物释放加快而对凝胶溶蚀没有明显影响。结论:药物释放主要取决于凝胶溶蚀,可通过调节处方中影响凝胶溶蚀及药物扩散的因素来控制药物从407凝胶中的释放。     

海藻酸钠骨架材料中药物释放的影响因素

目的以海藻酸钠为亲水骨架材料，考察药物从海藻酸钠骨架片中释放的体外影响因素。方法以茶碱为模型药物，采用直接压片法制备了茶碱海藻酸钠亲水骨架片，通过对骨架片膨胀性、吸水性以及溶蚀性的考察，研究了影响药物从海藻酸钠骨架材料中释放的体外因素。结果茶碱海藻酸钠骨架片的释药速率和释药机理与骨架片中海藻酸钠粘度、释放介质pH值、离子强度以及转速均有关。结论海藻酸钠能有效地控制骨架片中药物的释放，是一种优良的亲水骨架材料。     

Surface and transport properties of acrylic polymers influencing drug release from porous matrices

Three acrylic/methacrylic esters copolymers with different percentages of hydrophilic groups were used to prepare porous matrices containing aspirin as a drug model. The surface and transport properties of these matrices were studied by measuring the liquid/polymer contact angle and the liquid penetrability, whereas the porous structure was measured by mercury porosimetry. In the case of a non-wetting liquid, such as water, the penetration was found to be controlled by the intraparticle polymer diffusion, whereas for a wetting liquid the penetration was capillary driven.Consequently the drug release was dependent on the pore structure, i.e. the compaction pressure, in the case of a wetting liquid, whereas no pore structure influence was found in the case of water. Furthermore. whatever the copolymer used or the dissolution medium employed, the drug release was found √t -dependent suggesting a drug diffusion only through the interparticie pores.     

Factors affecting drug release from drug-coated granules prepared by fluidized-bed coating

The preparation of drug-coated core formulations where the drug is located on the surface of a lactose granule core, using a methylcellulose (MC) or a hydroxypropylmethylcellulose (HPMC) polymeric system with diphenhydramine hydrochloride as a model drug, was studied. The drug and the polymer were applied onto lactose granules using the fluidized-bed coating method. The intermittent spray conditions adopted were able to minimize aggregation of the granules and the spray drying of the coating liquid. A high coating efficiency of over 97% was obtained and the granules were evenly coated. In vitro drug release from the coated granules was shown to be dependent on the drug loading, hydrophilicity, adhesive properties, viscosity and total amount of the polymer in the drug-polymer coat. The effect of the air entrapped in the coated lactose granules on their release profiles is also discussed. These results have important implications for the design of drug-coated granules as a modified-release dosage form employing a water-soluble polymeric system.     

Factors affecting mechanism and kinetics of drug release from matrix-based oral controlled drug delivery systems

Matrix technologies have often proven popular among the oral controlled drug delivery technologies because of their simplicity, ease in manufacturing, high level of reproducibility, stability of the raw materials and dosage form, and ease of scale-up and process validation. Technological advancements in the area of matrix formulation have made controlled-release product development much easier than before, and improved upon the feasibility of delivering a wide variety of drugs with different physicochemical and biopharmaceutical properties. This is reflected by the large number of patents filed each year and by the commercial success of a number of novel drug delivery systems based on matrix technologies. Matrix-based delivery technologies have steadily matured from delivering drugs by first-order or square-root-of-time release kinetics to much more complex and customized release patterns. In order to achieve linear or zero-order release, various strategies that seek to manipulate tablet geometry, polymer variables, and formulation aspects have been applied. Various drug, polymer, and formulation-related factors, which influence the in situ formation of a polymeric gel layer/drug depletion zone and its characteristics as a function of time, determine the drug release from matrix systems. Various mathematical models, ranging from simple empirical or semi-empirical (Higuchi equation, Power law) to more complex mechanistic theories that consider diffusion, swelling, and dissolution processes simultaneously, have been developed to describe the mass transport processes involved in matrix-based drug release. Careful selection of an appropriate model for drug release provides insight to the underlying mass transport mechanisms and helps in predicting the effect of the device design parameters on the resulting drug-release rate. Thus, a basic understanding of release kinetics and appropriate mechanisms of drug release from matrix system and their inter-relationships may minimize the number of trials in final optimization, thereby improving formulation development processes.     

Formulation factors affecting the release of ezetimibe from different liquisolid compacts

Context: Liquisolid technique is one of the methods used to improve the dissolution rate of the poorly water soluble drugs utilizing non volatile liquids.Objectives: Enhancement of the release of ezetimibe from different liquisolid formulations.Materials and Methods: Four liquid vehicles were used to prepare the liquid medications with different drug concentrations. The interaction between the drug and the excipients in liquisolid powders were characterized by DSC, X-ray, FTIR and SEM. Furthermore, the powder characteristics were evaluated by Carr’s Index and powder wetting time determinations, respectively. All prepared formulations were compressed at different pressures to end with the same constant porosity and the tablets were evaluated by different tests and compared with conventional formula. Results and Discussion: No interaction had been detected in all liquisolid formulations as shown in the results of XRD, FTIR, DSC and SEM. In addition to that, all liquisolid compacts had expressed faster dissolution profiles compared with that of conventional formula. Conclusion: The dissolution rate was affected by the drug concentration, solubility of the drug in the liquid vehicle and type of carrier. In addition, the presence of the liquid vehicle has been found to affect the mechanical properties of the liquisolid formulations.