Optimization of furosemide liquisolid tablets preparation process leading to their mass and size reduction

The great number of drug substances currently used in solid oral dosage forms is characterized by poor water solubility. Therefore, various methods of dissolution rate enhancement are an important topic of research interest in modern drug technology. The purpose of this study was to enhance the furosemide dissolution rate from liquisolid tablets while maintaining an acceptable size and mass. Two types of dibasic calcium phosphate (FujicalinÆ/EmcompressÆ) and microcrystalline cellulose (VivapurÆ 102/VivapurÆ 12) were used as carriers and magnesium aluminometasilicate (NeusilinÆ US2) was used as a coating material. The flowable liquid retention potential for those excipients was tested by measuring the angle of slide. To evaluate the impact of used excipients on tablet properties fourteen tablet formulations were prepared. It was found that LS2 tablets containing spherically granulated dibasic calcium phosphate and magnesium aluminometasilicate exhibit the best dissolution profile and mechanical properties while tablets composed only with NeusilinÆ US2 was characterized by the smallest size and mass with preserved good mechanical properties and furosemide dissolution

Printing techniques : recent developments in pharmaceutical technology

In the last few years there has been a huge progress in a development of printing techniques and their application in pharmaceutical sciences and particularly in the pharmaceutical technology. The variety of printing methods makes it necessary to systemize them, explain the principles of operation, and specify the possibilities of their use in pharmaceutical technology. This paper aims to review the printing techniques used in a drug development process. The growing interest in 2D and 3D printing methods results in continuously increasing number of scientific papers. Introduction of the first printed drug SpritamÆ to the market seems to be a milestone of the 3D printing development. Thus, a particular aim of this review is to show the latest achievements of the researchers in the field of the printing medicines

Fused deposition modeling 3D printing as a method for manufacturing personalized medicines

Additive manufacturing techniques, especially methods based on the deposition of thermoplastic material such as Fused deposition modeling (FDM), are gaining more and more applications. Due to the large variety of materials used and the quick ability to produce small batches of products in accordance with the computer project, these methods are considered as a method of dosage forms manufacturing both on an industrial scale as well as in small batches. Numerous scientific studies related to the printing of dosage forms of various structures have been published in recent years. These studies concern both preparations for oral administration, such as tablets and capsules with modified and immediate release of the active pharmaceutical ingredient (API), as well as intraocular dosage forms and wound dressings. In the case of the FDM method, the printing process is preceded by the material preparation step. It consists of the preparation of a drug-loaded filament in the hot-melt extrusion process. After feeding the filament into the printer's head, it is re-heated, liquefied, and precisely deposited on the printer's table in order to reproduce a spatial structure according to the computer design. The filaments used in the printing process of the dosage form should be characterized by, among others: appropriate mechanical strength, high diameter uniformity, and long-term stability. Apart from thermoplastic polymers, other excipients are also used in the composition of the formulation, i.e., disintegrants, plasticizers, and compounds inhibiting the API phase transformations in the polymer matrix. Printed dosage forms are often characterized by a complex internal spatial structure. For this reason, the API release depends not only on the properties of the excipients used, but especially on printouts’ surface area and porosity, as well as the shape and infill density. In addition, conditions during the extrusion and 3D printing processes may result in the dissolution of API in the polymer carrier and accelerate its dissolution rate

Complications in recipients of cardioverter-defibrillator or cardiac resynchronization therapy: Insights from Silesian Center Defibrillator registry

Background: Current real-life information from all-comers registries from middle and east Europe about the incidence and type of complications during long-term follow-up of patients with cardioverters-defibrillators (ICD) and cardiac resynchronization devices-defibrillators (CRT-D) is still insufficient. The aim of the study was to assess the incidence and determinants of short- and long-term complications related to implantable ICD and CRT-D. Methods: We studied 1,105 recipients hospitalized in our center in 2009–2013, followed for a mean of 2.4 years (total of 2,652 patient-years). The independent association between ICD and CRT-D recipients’ and implantation-procedures’ characteristics with the incidence of complications was analyzed using multivariable Cox regression analysis. Results: In 2-month post-procedural period, 124 (11.2%) patients developed complications. Independent predictors of short-term complications (within 2 months) were: atrial fibrillation, dual chamber ICD implantation, and use of antiplatelet therapy or coumarin. Twenty-seven (2.44%) patients experienced complications, mostly lead-related (n = 21). Independent predictors of long-term complications (2–12 months after implantation) were atrial fibrillation and dual chamber ICD implantation. Conclusions: Despite significant technological progress and operators’ experience, the occurrence of complications in ICD and CRT-D recipients is still substantial. Majority of complications are recorded in the early post-implantation phase. Analysis of independent predictors of complications seem to be essential in helping to reduce adverse events in the future and strongly supports the need for routine follow-up.  

Profiling the Proteome of Cyst Nematode-Induced Syncytia on Tomato Roots

Cyst nematodes are important herbivorous pests in agriculture that obtain nutrients through specialized root structures termed syncytia. Syncytium initiation, development, and functioning are a research focus because syncytia are the primary interface for molecular interactions between the host plant and parasite. The small size and complex development (over approximately two weeks) of syncytia hinder precise analyses, therefore most studies have analyzed the transcriptome of infested whole-root systems or syncytia-containing root segments. Here, we describe an effective procedure to microdissect syncytia induced by Globodera rostochiensis from tomato roots and to analyze the syncytial proteome using mass spectrometry. As little as 15 mm2 of 10-µm-thick sections dissected from 30 syncytia enabled the identification of 100–200 proteins in each sample, indicating that mass-spectrometric methods currently in use achieved acceptable sensitivity for proteome profiling of microscopic samples of plant tissues (approximately 100 µg). Among the identified proteins, 48 were specifically detected in syncytia and 7 in uninfected roots. The occurrence of approximately 50% of these proteins in syncytia was not correlated with transcript abundance estimated by quantitative reverse-transcription PCR analysis. The functional categories of these proteins confirmed that protein turnover, stress responses, and intracellular trafficking are important components of the proteome dynamics of developing syncytia

Molecular disorder of bicalutamide : amorphous solid dispersions obtained by solvent methods

The effect of solvent removal techniques on phase transition, physical stability and dissolution of bicalutamide from solid dispersions containing polyvinylpyrrolidone (PVP) as a carrier was investigated. A spray dryer and a rotavapor were applied to obtain binary systems containing either 50% or 66% of the drug. Applied techniques led to the formation of amorphous solid dispersions as confirmed by X-ray powder diffractometry and differential scanning calorimetry. Moreover, solid–solid transition from polymorphic form I to form II was observed for bicalutamide spray dried without a carrier. The presence of intermolecular interactions between the drug and polymer molecules, which provides the stabilization of molecularly disordered bicalutamide, was analyzed using infrared spectroscopy. Spectral changes within the region characteristic for amide vibrations suggested that the amide form of crystalline bicalutamide was replaced by a less stable imidic one, characteristic of an amorphous drug. Applied processes also resulted in changes of particle geometry and size as confirmed by scanning electron microscopy and laser diffraction measurements, however they did not affect the dissolution significantly as confirmed by intrinsic dissolution study. The enhancement of apparent solubility and dissolution were assigned mostly to the loss of molecular arrangement by drug molecules. Performed statistical analysis indicated that the presence of PVP reduces the mean dissolution time and improve the dissolution efficiency. Although the dissolution was equally affected by both applied methods of solid dispersion manufacturing, spray drying provides better control of particle size and morphology as well as a lower tendency for recrystallization of amorphous solid dispersions

How does the CO2 in supercritical state affect the properties of drug-polymer systems, dissolution performance and characteristics of tablets containing bicalutamide?

The increasing demand for novel drug formulations has caused the introduction of the supercritical fluid technology, CO2 in particular, into pharmaceutical technology as a method enabling the reduction of particle size and the formation of inclusion complexes and solid dispersions. In this paper, we describe the application of scCO2 in the preparation of binary systems containing poorly soluble antiandrogenic drug bicalutamide and polymeric excipients, either Macrogol 6000 or Poloxamer®407. The changes in the particle size and morphology were followed using scanning electron microscopy and laser di raction measurements. Di erential scanning calorimetry was applied to assess thermal properties, while X-ray powder di ractometry was used to determine the changes in the crystal structure of the systems. The dissolution of bicalutamide was also considered. Binary solid dispersions were further compressed, and the attributes of tablets were assessed. Tablets were analyzed directly after manufacturing and storage in climate chambers. The obtained results indicate that the use of supercritical CO2 led to the morphological changes of particles and the improvement of drug dissolution. The flowability of blends containing processed binary systems was poor; however, they were successfully compressed into tablets exhibiting enhanced drug release

Compression-Induced Phase Transitions of Bicalutamide

The formation of solid dispersions with the amorphous drug dispersed in the polymeric matrix improves the dissolution characteristics of poorly soluble drugs. Although they provide an improved absorption after oral administration, the recrystallization, which can occur upon absorption of moisture or during solidification and other formulation stages, serves as a major challenge. This work aims at understanding the amorphization-recrystallization changes of bicalutamide. Amorphous solid dispersions with poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) were obtained by either ball milling or spray drying. The applied processes led to drug amorphization as confirmed using X-ray diffraction and differential scanning calorimetry. Due to a high propensity towards mechanical activation, the changes of the crystal structure of physical blends of active pharmaceutical ingredient (API) and polymer upon pressure were also examined. The compression led to drug amorphization or transition from form I to form II polymorph, depending on the composition and applied force. The formation of hydrogen bonds confirmed using infrared spectroscopy and high miscibility of drug and polymer determined using non-isothermal dielectric measurements contributed to the high stability of amorphous solid dispersions. They exhibited improved wettability and dissolution enhanced by 2.5- to 11-fold in comparison with the crystalline drug. The drug remained amorphous upon compression when the content of PVP/VA in solid dispersions exceeded 20% or 33%, in the case of spray-dried and milled systems, respectively.Polish National Science Centre 2015/16/W/NZ7/0040