1,720,983 research outputs found
Formulation and release behavior of doxycycline- alginate complex hydrogel microparticles embedded into Pluronic F127 thermogels for doxycycline intradermal sustained delivery
No full textPurpose. The aim of this work was the formulation and characterization of a new doxycycline (Dox)- alginate complex hydrogel microparticles embedded into Pluronic F127 thermogel for doxycycline intradermal sustained delivery.
Methods. Batches of Dox-Alginate complex MP were prepared by direct injection of a solution of the drug into a 1.5% polymer solution upon silverson stirring. The MP were recovered and freeze-dried. The hydrogel MP were successively formed by dispersing the MP into a 1.2% CaCl2 solution. The MP were characterized in terms of size, drug content, and release behavior by HPLC. Free Dox and hydrogel MP were then embedded into PF127, PF127-HPMC, and PF127-Methocel thermogels. The thermogels were produced by dissolving PF127 and HPMC or Methocel in phosphate buffer at 4°C and were characterized in terms of gelling time, morphology and release behavior. A target release period of 6-7 days was considered optimal.
Results. Dox-Alginate complexation occurred spontaneously either in water or phosphate buffer upon mixing. The hydrogel MP were about 20 μm in size with 90% of the population < 59 μm. Drug content was about 35% w/w for all the preparations. Dox was released fast from the MP with a 90% after just 1-2 days. An expected faster release was also observed for free Dox from the thermogels with 80-90% of drug released after 3.5-4 hours, even in the presence of 1% HPMC or Methocel. The release was much slower and sustained after embedding the MP into PF127 and PF127-HPMC thermogels. In particular, the PF127-HPMC thermogel showed an almost linear release reaching 80% after 3 days and 90% up to 6 days.
Conclusions. Although a further characterization and formulation assessment is needed to optimize MP characteristics, Dox-Alginate loaded hydrogel MP, when embedded into a PF127-HPMC thermogel, seem to be promising in order to achieve a 7 days sustained release formulation for Dox intradermal sustained delivery
A Short Term Quality Control Tool for Biodegradable Microspheres
No full textAccelerated in vitro release testing methodology has been developed as an indicator of product performance to be used as a discriminatory quality control (QC) technique for the release of clinical and commercial batches of biodegradable microspheres. While product performance of biodegradable microspheres can be verified by in vivo and/or in vitro experiments, such evaluation can be particularly challenging because of slow polymer degradation, resulting in extended study times, labor, and expense. Three batches of Leuprolide poly(lactic-co-glycolic acid) (PLGA) microspheres having varying morphology (process variants having different particle size and specific surface area) were manufactured by the solvent extraction/evaporation technique. Tests involving in vitro release, polymer degradation and hydration of the microspheres were performed on the three batches at 55°C. In vitro peptide release at 55°C was analyzed using a previously derived modification of the Weibull function termed the modified Weibull equation (MWE). Experimental observations and data analysis confirm excellent reproducibility studies within and between batches of the microsphere formulations demonstrating the predictability of the accelerated experiments at 55°C. The accelerated test method was also successfully able to distinguish the in vitro product performance between the three batches having varying morphology (process variants), indicating that it is a suitable QC tool to discriminate product or process variants in clinical or commercial batches of microspheres. Additionally, data analysis utilized the MWE to further quantify the differences obtained from the accelerated in vitro product performance test between process variants, thereby enhancing the discriminatory power of the accelerated methodology at 55°C. © 2014 American Association of Pharmaceutical Scientists
In vitro–in vivo correlation from lactide-co-glycolide polymeric dosage forms
No full textThe objective of this study was to compare the in vitro behavior of four long-acting subcutaneous ris- peridone formulations with in vivo performance, with the intent of establishing an IVIVC. Two copolymers of PLGA (50:50 and 75:25) were used to prepare four microsphere formulations of risperidone, an atypical antipsychotic. In vitro behavior was assessed at the physiological temperature (37 °C) using the ‘modified dialysis’ technique. The in vitro release profile demon- strated rank order behavior with Formulations A and B, prepared using the 50:50 copolymer, exhibiting rapid drug release, while Formulations C and D, prepared using
75:25 PLGA, released drug in a slower manner. In vivo profiles were obtained by two approaches, i.e., deconvo- lution using the Nelson–Wagner equation (the FDA rec- ommended approach) and using fractional AUC. With both in vivo approaches, the 50:50 PLGA preparations released drug faster than the 75:25 PLGA microspheres, exhibiting the same rank order observed in vitro. Addi- tionally, profiles for the four formulations obtained using the deconvolution approach were nearly superimposable with fractional AUC, implying that the latter procedure could be used as a substitute for the Nelson–Wagner method. A comparison of drug release profiles for the four formulations revealed that in three of the four formula- tions, in vivo release was slightly faster than that in vitro, but the results were not statistically significant (P [ 0.0001). An excellent linear correlation (R2 values between 0.97 and 0.99) was obtained when % in vitro release for each formulation was compared with its cor- responding in vivo release profile, obtained by using fraction absorbed (Nelson–Wagner method) or fractional AUC. In summary, using the four formulations that exhibited different release rates, a Level A IVIVC was established using the FDA-recommended deconvolution method and fractional AUC approach. The excellent relationship between in vitro drug release and the amount of drug absorbed in vivo in this study was corroborated by the nearly 1:1 correlation (R2 greater than 0.97) between in vitro release and in vivo performance. Thus, the results of the current study suggest that proper selection of an in vitro method to assess drug release from long-acting injectables will aid in obtaining a Level A IVIVC
Accelerated polymer biodegradation of risperidone poly(D, L-lactide-co-glycolide) microspheres
No full textThe influence of a tertiary amine, namely risperidone (pKa = 7.9) on the degradation of poly(D, L lactide-co-glycolide) (PLGA) microspheres was elucidated. Risperidone and blank microspheres were fabricated at two lactide/glycolide ratios, 65:35 and 85:15. The microspheres were characterized for drug loading by high-performance liquid chromatography, particle size by laser diffractometry, and surface morphology by scanning electron microscopy. Polymer degradation studies were carried out with drug-loaded microspheres and blank microspheres in presence of free risperidone in 0.02 M PBS containing 0.02% Tween®80 at 37°C. Molecular weight was monitored by gel permeation chromatography. Risperidone and blank microspheres had similar size distribution and were spherical with a relatively nonporous smooth surface. The presence of risperidone within the microspheres enhanced the hydrolytic degradation in both polymeric matrices with faster degradation occurring in 65:35 PLGA. The molecular weight decreased according to pseudo-first-order kinetics for all the formulations. During the degradation study, the surface morphology of drug-loaded microspheres was affected by the presence of risperidone and resulted in shriveled microspheres in which there appeared to be an intrabatch variation with the larger microspheres being less shriveled than the smaller ones. When blank microspheres were incubated in free risperidone solutions, a concentration-dependent effect on the development of surface porosity could be observed. Risperidone accelerates the hydrolytic degradation of PLGA, presumably within the microenvironment of the drug-loaded particles, and this phenomenon must be taken into consideration in designing PLGA dosage forms of tertiary amine drugs
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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