Ethylene vinyl acetate as matrix for oral sustained release dosage forms produced via hot-melt extrusion

Different ethylene vinyl acetate grades (EVA9, EVA15, EVA28 and EVA40 having a VA content of 9%, 15%, 28% and 40%, respectively) were characterized via differential scanning calorimetry. Glass transition temperature (T_g), polymer crystallinity, melting point and polymer flexibility were positively influenced by the vinyl acetate content. The processability of EVA-based formulations produced by means of hot-melt extrusion (2 mm die) was evaluated in function of VA content, extrusion temperature (60–140 °C) and metoprolol tartrate (MPT, used as model drug) concentration (10–60%). Matrices containing 50% MPT resulted in smooth-surfaced extrudates, whereas at 60% drug content severe surface defects (shark skinning) were observed. Drug release from EVA/MPT matrices (50/50, w/w) was affected by the EVA grades: 90% after 24 h for EVA15 and 28, while EVA9 and EVA40 formulations released 80% and 60%, respectively. Drug release also depended on drug loading and extrusion temperature. For all systems, the total matrix porosity (measured by X-ray tomography) was decreased after dissolution due to elastic rearrangement of the polymer. However, the largest porosity reduction was observed for EVA40 matrices as partial melting of the structure (melt onset temperature: 34.7 °C) also contributed (thereby reducing the drug release pathway and yielding the lowest release rate from EVA40 formulations).The Simulator of the Human Intestinal Microbial Ecosystem (SHIME) used to evaluate the stability of EVA during gastrointestinal transit showed that EVA was not modified during GI transit, nor did it affect the GI ecosystem following oral administration.     

Hydrodynamically balanced systems as sustained release dosage forms for propranolol hydrochloride

Sustained release hydrodynamically balanced capsules (HBS) of propranolol.HCl have been prepared and evaluated in vitro. Data to support the mechanism of drug release from the HBS capsule are also presented. Floating behaviour of the HBS capsule has also been seen in vivo with the help of endoscopy.     

Solid lipid microparticles as a sustained release system for pulmonary drug delivery.

The controlled release of drugs for pulmonary delivery is a research field which has been so far rather unexploited but is currently becoming increasingly attractive. The introduction part of this research article first details the potential advantages of solid lipid microparticles (SLMs) as drug carrier compared to liposomes and polymeric microspheres. The aim of this work is to use SLMs to impart a sustained release profile to a model drug, salbutamol acetonide (SA). SA was synthesized from salbutamol in order to increase the lipophilicity of this molecule and thereby to increase its incorporation efficiency into SLMs. SA-loaded SLMs were then produced by a hot emulsion technique followed by high-shear homogenisation and the manufacturing parameters were optimized using the experimental design methodology in order to reach a suitable particle size for pulmonary administration. Scanning electron micrographs showed that SLMs are spherical, have a smooth surface and that SA crystallizes outside of the particles when the drug loading is higher than 20%. This was confirmed by X-ray diffraction. SA in vitro release study from SLMs showed that the release rate increased with SA loading but remained in every case lower than the dissolution rate of pure SA.     

缓释控释制剂的释放度测定方法的研究进展

目的　介绍缓、控释制剂的体外释放度测定方法 ,使其能更好地模拟体内状态。方法　综述最近的中外文献中有关缓释、控释制剂的体外释放度测定实验方法 ,实验条件的选择及影响因素。结果　体外释放度实验条件如释放介质的 pH值、离子强度、增溶剂、表面活性剂和释放仪器等可影响缓、控释制剂的体外释放度。结论　根据不同药物选择尽可能接近体内状态的方法     

缓释控释制剂的释放度测定方法的研究进展

目的介绍缓、控释制剂的体外释放度测定方法,使其能更好地模拟体内状态.方法综述最近的中外文献中有关缓释、控释制剂的体外释放度测定实验方法,实验条件的选择及影响因素.结果体外释放度实验条件如释放介质的pH值、离子强度、增溶剂、表面活性剂和释放仪器等可影响缓、控释制剂的体外释放度.结论根据不同药物选择尽可能接近体内状态的方法.     

Oral controlled release dosage forms. A review

When a drug meets the criteria which make incorporation into a controlled release dosage form rational, a proper dosage form has to be selected. Oral controlled release products, available on the Dutch market, are referred to in discussing the various methods used to control drug release by galenical means in order to achieve a prolonged therapeutic effect. The effects of some physiological variables of the alimentary tract on drug delivery from the various dosage forms, especially with regard to formulation and design, are reviewed.     

Influence of plasticizer level on the drug release from sustained release film coated and hot-melt extruded dosage forms

In the current study, the influence of plasticizer level on drug release was investigated for solid dosage forms prepared by hot-melt extrusion and film coating. The properties of two highly water-soluble compounds, diltiazem hydrochloride (DTZ) and chlorpheniramine maleate (CPM), and a poorly water-soluble drug, indomethacin (IDM), were investigated in the melt extrudates containing either Eudragit RSPO or Eudragit RD 100 and triethyl citrate (TEC) as the plasticizer. In addition, pellets containing DTZ were film coated with Eudragit RS 30D and varying levels of TEC using a fluidized bed coating unit. Differential scanning calorimetry (DSC) demonstrated that both CPM and IDM exhibited a plasticization effect on the acrylic polymers, whereas no plasticizing effect by DTZ on Eudragit RSPO was observed. Thermogravimetric analysis (TGA) was used to investigate the thermal stability of the DTZ, Eudragit RSPO and TEC at 140 degrees C, the maximum temperature used in the hot-melt extrusion process. The chemical stability of DTZ and IDM in the extrudate following hot-melt processing was determined by high pressure liquid chromatography (HPLC). Drug release rates of both DTZ and CPM from hot-melt extrudates increased with an increase in the TEC level in the formulations, while the release rate of DTZ from the Eudragit RS 30D-coated pellets decreased with an increase in TEC in the coating dispersion. This phenomenon was due to the formation of a reservoir polymeric structure as a result of the thermal stress and shear stress involved in the hot-melt extrusion process regardless of the TEC level. In contrast, coalescence of the polymer particles in the film coating process was enhanced with higher levels of TEC, as demonstrated by scanning electron microscopy (SEM). The addition of TEC (0% to 8%) in the IDM hot-melt extrudate formulation had no influence on the drug release rate as the drug release rate was controlled by drug diffusion through the inside of the polymeric materials rather than between the polymer particles.     

Active compounds release from semisolid dosage forms

The aim of this paper is to review all the aspects of the in vitro release testing (IVRT) from semisolid dosage forms. Although none of the official dissolution methods has been specified for use with semisolid dosage forms, their utility for assessing release rates of drugs from semisolid dosage forms has become a topic of considerable interest. One can expect to overcome such complexity in the future, when the official “Topical and Transdermal Drug Products—Product Performance Tests” will be published in an issue of the Pharmacopeial Forum. Many factors such as type of the dissolution medium, membrane, temperature, and speed have an influence on the mechanism and kinetics of the release testing from gels, creams, and ointments; therefore, those parameters have been widely discussed.     

Attitude and perception of patients and health care practitioners toward oral sustained release dosage forms in Palestine

Aim

To evaluate the knowledge of health professionals in Palestine regarding the advantages of sustained release dosage forms (SRDFs) over conventional therapy.

Methods

Data were gathered from a questionnaire that was handed out to community pharmacists, physicians and patients. Pharmaceutical industry decision makers were enrolled in this study. Data were analyzed using the SPSS.

Results

Pharmacists (92.9%) and 89.2% of physicians thought that SRDFs improve patient compliance. 81.5% of pharmacists and 77% of physicians were in agreement regarding the capacity of SRDFs to maintain therapeutic activity during night. In this study, 81.5% of pharmacists and 81% of physicians believed that SRDFs provide further advantage with psychiatric patients who forget to take their medications. Pharmacists (63.1%) and only 63.5% of physicians believed that SRDFs yield a time saving for nurses who use SRDFs in hospital. Only 45.3% of physicians and 43.4% of pharmacists thought that SRDFs result in cost saving due to better disease management. Pharmacists (95.2%) and 95.9% of physicians agreed that SRDFs could be the right choice for faith patient’s who must take their medication during the month of Ramadan. Pharmacists (66.7%) and 50.7% of physicians recognize that SRDFs may be unsafe if they are improperly formulated. Bad swallowing was also recognized as inconveniences of SRDFs by 67.9% of pharmacists and 57.3% of physicians. Given the above advantages, 75% of patients showed economical problems regarding the cost of the single course therapy of SRDFs and 100% of interviewed patients were enthusiastic about the advantage of SRDFs during Ramadan.

Conclusion

The advantages of SRDFs are not completely understood by Palestinian health professionals. Pharmaceutical industries should pay more attention to the development and advertising of SRDFs due to the valuable advantages of these dosage forms.     

剂量分割法评价甘氨酸茶碱钠缓释片体内释放度及其体内外相关性

目的以剂量分割法分析甘氨酸茶碱钠缓释片(STG-ST,平喘药)的体内外释放相关性,并与Wagner-Nelson法进行比较。方法根据剂量分割法原理,计算STG-ST体内释放动力学;以Wagner-Nelson法,采用不同吸收速率常数计算STG-ST的体内吸收度。结果Wagner-Nelson法计算药物吸收度时,直接使用缓控释制剂的表观动力学参数,容易导致方法学错误;而剂量分割法得到的体内释放度与体外释放度相关性良好。结论无需注射剂作为参比,剂量分割法适合于缓释/控释制剂体内外相关性评价。     

Immediate drug release from solid oral dosage forms

Fast drug release from solid dosage forms requires a very fast contact of the vast majority of the drug particles with the solvent; this, however, is particularly delayed in tablets and granulations. Starch and cellulose substances favor the matrix disintegration during the starting phase and the generation of the effective dissolution surface of the drug substance, thereby. To investigate the very complex interrelation between the functionality of commonly used excipients and the structural effects of the production processes, wettability, porosity, water uptake, and drug release rates of several ketoprofen-excipient preparations (powder blends, granulations, tablets) were measured. Significant linear correlation between these parameters, however, was not achieved; only qualitative tendencies of the effects could be detected. In consequence, a general mathematical model describing the mechanistic steps of drug dissolution from solid dosage forms in a fully correct way was not realized. However, the time-dependent change of the effective dissolution surface follows stochastic models: a new dissolution equation is based on the differential Noyes-Whitney equation combined with a distribution function, e.g. the lognormal distribution, and numerically solved with the software system EASY-FIT by fitting to the observations. This new model coincides with the data to a considerably higher degree of accuracy than the Weibull function alone, particularly during the starting, matrix disintegration, and end phases. In combination with a procedure continuously quantifying the dissolved drug, this mathematical model is suitable for the characterization and optimization of immediate drug release by the choice and modification of excipients and unit operations. The interdependence of some characteristic effects of excipients and production methods is discussed.     

化学药物口服缓控释制剂体内外相关性研究

《口服缓控释制剂药学研究技术指导原则》中多处提到了体内外相关性,文中试图通过对体内外相关性(IVIVC)的定义、创建、评价和应用等方面的介绍,对IVIVC可行性的评估以及IVIVC与生物豁免和释放度质量标准的关系的讨论,帮助研发者理解该指导原则的相关内容。     

Magnetic resonance imaging of controlled release pharmaceutical dosage forms

Magnetic resonance imaging offers us a powerful non-invasive method for picturing events inside controlled-release dosage forms. It allows us to observe, follow and measure important processes, such as hydration and diffusion, that can contribute directly to the process of drug release. The potential of this technique for increasing our understanding of drug release mechanisms, and the behaviour of dosage forms in vitro and in vivo is only beginning to be exploited. The unique information obtained from MRI studies will provide important detailed knowledge in problem solving and formulation development.     

Percutaneous release of caffeine from microemulsion, emulsion and gel dosage forms.

The transport of caffeine to the hypodermis by an alcohol-free o/w microemulsion was investigated and compared with an aqueous gel and an o/w emulsion. The microemulsion was well characterized and in vitro diffusion measurements through pig skin having the hypodermis either kept or removed were performed in static Franz cells. The microemulsion allowed delivery of a large fraction of the caffeine in the hypodermis: 23% of caffeine reached the hypodermis after 24h diffusion, 1.3-fold larger than from the emulsion and gel dosage forms. Half this amount was stored in the hypodermis, the other half continuing its diffusion to the receptor compartment of the Franz cell.