Promoção do aumento da solubilidade de fármacos pouco solúveis para a sua administração oral em formas farmacêuticas de libertação imediata ou controlada

Tese de doutoramento, Farmácia (Tecnologia Farmacêutica), 2009, Universidade de Lisboa, Faculdade de FarmáciaDisponível no document

Teoria da percolação aplicada à produção de comprimidos

Dissertação de Mestrado em Tecnologia Farmacêutica, área de especialização em Farmacotecnia, apresentada à Faculdade de Farmácia da Universidade do Port

Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

Lactose monohydrate flow characterization using shear cell method

The flow properties of pharmaceutical powders have a great importance in the manufacturing of solid dosage forms. In order to ensure the performance in the production line this parameter must be determined. There are several methods described in European Pharmacopeia that are used to measure these properties. Some of them were used in this study and the results obtained from conventional methods (Conv) and shear cell using the powder flow tester (PFT) showed differences that were more evident in fractions with smaller particle size (F < 63) and for bulk powder (FTotal). The various powder behaviors showed to be related with the size of the particles. An increase of the ffc (Flow Index) was observed with the increase of the particle size. It was also found for the different fractions that the ffc always increases with increasing major principal consolidation stress (σ1). This study shown to be predictive because it also allowed the behavior profiles of other LactMN fractions to be known by interpolation of the median size (Dv50) or σ1 values ranged between the studied intervals. Furthermore, it was also observed that ffc of the FTotal was similar to the F < 63, showing the same behavior under σ1. The occurrence of caking was not observed.This work was supported by the Applied Molecular Biosciences Unit-UCIBIO, which is financed by national funds from FCT/MCTES (UID/Multi/04378/2019). The authors thank Dra. Teresa Malta and Atral, S.A., for the kindly supplying of the lactose monohydrate, that made this work possible.info:eu-repo/semantics/publishedVersio

Flow characterization of a pharmaceutical excipient using the shear cell method

The powders used in the production of solid dosage forms must have ability to flow that allows their industrial processing. Although this property has been studied for most of the powders, in this study non-expected flow behaviors were observed for the model excipient used, Microcrystalline Cellulose (MCC). Several fractions with different sizes were fractioned by sieving of the model excipient and its flow behaviors were analyzed by different methods. The shear cell results showed an increase of the flowability index (ffc) with the increase of the particle size and consolidation stress. Some related information has been referenced in the literature, however, in this work it was shown for different size fractions that the ffc decreased above a certain consolidation stress value (2000–4000 N/m2). The explanation of this phenomenon is based on the increase of cohesion. Furthermore, it was also observed that the fractions with sizes between 125–180 µm present a ffc higher than bulk powder (FTotal) with similar percentile (DV50) indicating that this index is dependent on the size of the particles and also on its size distribution range. Thus, it can be affirmed that more homogeneous samples in size and with a narrower distribution present a better ffc.The authors would like to thank Dr. Teresa Malta and Atral, S.A., for the kindly offer of the cellulose microcrystalline, that made this work possible. This work was supported by the Applied Molecular Biosciences Unit-UCIBIO which is financed by national funds from FCT/MCTES (UID/Multi/04378/2019).info:eu-repo/semantics/publishedVersio

Influence of the Glidant on Diluent Flow Characterization Using Shear Cell Method

The aim of this study was to compare the bulk lactose flow behavior with a defined fraction with smaller particles obtained by sieving from the bulk lactose and to evaluate the effect of a glidant addition on both samples. These powders showed, in a previous work, similar flow indexes (ffc) that motivated the addition of colloidal silicon dioxide in order to observe if there were any changes in their flow behaviors. Methods To evaluate this effect on the diluent flow behavior, the methods described in the European Pharmacopeia were used. Results The results obtained from conventional methods and shear cell methods (using the Powder Flow Tester) were compared, and they showed evident differences in the bulk and tapped densities values and flow classifications. The lactose monohydrate (FTotal) and lactose with particles smaller than 63 μm (F < 63) analyzed in a previous study presented similar ffc. To these pure powders a glidant was added, in increasing proportion (0.25—1.00%). The results obtained for all powders with colloidal silicon dioxide showed an improvement in its flow behaviors in comparison with pure powders. Conclusion All the parameters studied showed an evident effect of the glidant used. For the same amount of glidant, the F < 63 presented worse flow profiles than FTotal because its particles have a larger surface area. The FTotal + 0.25 flow profile was more similar to the F < 63 + 0.50 flow profile than F < 63 + 0.25 flow profile. For both powders, the maximum amount of glidant that produces effect was 1.00% for F < 63 and 0.75% for FTotal, respectively. In all powders, the occurrence of caking was not observed.The authors would like to thank Dra. Teresa Malta and Atral, S.A., for the kindly supplying of the lactose monohydrate, that made this work possible. This work was supported by the Applied Molecular Biosciences Unit-UCIBIO, which is financed by national funds from FCT/MCTES (UID/Multi/04378/2019).info:eu-repo/semantics/publishedVersio

Starch flow behavior alone and under different glidants action using the shear cell method

The objective of this work was to analyze the flow behavior of a commonly used filler (pregelatinised starch) and the effect of two of the most used lubricants (talc and colloidal silicon dioxide). The studies were carried out according to the conventional methods (Angle of Repose, Bulk and Tapped densities and from these the Compressibility Index) and shear cell methods (Brookfield Powder Flow Tester apparatus) described in European Pharmacopeia (Ph. Eur.). The results showed some surprising and unexpected values for the flow behavior of this filler under influence of the methods and the used glidants. Regarding pure starch and mixtures containing talc, the flow behavior was similar between them and the Flow Index (ffc) values varied between 1.8 and 4 (very cohesive and cohesive) as consolidation stress (σ1) increased. In this case, the glidant effect was not observed. However, for the mixtures of starch with colloidal silicon dioxide this effect was observed providing Flow Index (ffc) values between 2.6 and 8.9 (cohesive and easy-flowing) as consolidation stress (σ1) increased. Other parameters that are also used to characterize flow properties, more specifically, within silos, chutes and hoppers, such as effective angle of internal friction (φe), effective angle of wall friction (φx), critical arching and critical rathole values, provided similar information. Based in the obtained results from all tests it can be said that the talc did not induce improvement on the starch flow behavior in the used conditions in opposition to the effect produced by colloidal silicon dioxide.info:eu-repo/semantics/publishedVersio