http://hdl.handle.net/10451/3097 2013-05-18T01:36:23Z 2013-05-18T01:36:23Z Salústio, Paulo José Pontes, Patrícia Conduto, Cláudia Sanches, Inês Carvalho, Catarina Arrais, João Cabral Marques, Helena M http://hdl.handle.net/10451/8157 2013-04-02T14:09:35Z 2011-09-27T00:00:00Z

Title: Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release Authors: Salústio, Paulo José; Pontes, Patrícia; Conduto, Cláudia; Sanches, Inês; Carvalho, Catarina; Arrais, João; Cabral Marques, Helena M Abstract: 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.

2011-09-27T00:00:00Z Salústio, Paulo Feio, Gabriel Figueirinhas, João Cabral-Marques, Helena Costa, Paulo Pinto, Jão http://hdl.handle.net/10451/8153 2013-04-02T13:41:53Z 2012-01-01T00:00:00Z

Title: Release profile of ibuprofen in β-cyclodextrin complexes from two different solid dosage forms Authors: Salústio, Paulo; Feio, Gabriel; Figueirinhas, João; Cabral-Marques, Helena; Costa, Paulo; Pinto, Jão Abstract: The objective of this work was to develop solid dosage forms using powders containing inclusion complexes (ibuprofen with β-cyclodextrin) which were used to produce tablets (direct compression without additional excipients) and pellets (extrusion/spheronization) from wet mass containing 40% (w/w) of microcrystalline cellulose. The pellets also demonstrated that during preparation of the wet mass, the inclusion process occurred in a same yield that when pre-complexation was used. The particles characteristics were evaluated after being obtained through different complexation methods. The results showed that the tensile strength and profile dissolution were as expected for both dosage forms. Tablets containing inclusion complexes showed higher solubility when compared with a reference formulation and with two commercial formulations. The ibuprofen released from the two pellets formulations didn’t show relevant differences between them. The drug released was analyzed considering different dissolution parameters. The advantages of these new methodologies can be summarized as: (a) tablets were produced at a lower cost for the total process; and (b) in the pellet´s preparation there was no need of the previous complexation method resulting in a decrease in time and energy required.

2012-01-01T00:00:00Z Ramos, Margarida Salústio, Paulo Serralheiro, Luísa Frazão, Fátima Marques, Helena http://hdl.handle.net/10451/3863 2011-08-08T01:28:06Z 2010-10-28T00:00:00Z

Title: Stability and enzymatic studies with omeprazole: hydroxypropyl-β-cyclodextrin Authors: Ramos, Margarida; Salústio, Paulo; Serralheiro, Luísa; Frazão, Fátima; Marques, Helena Abstract: Omeprazole (OME) exhibits low stability to light, heat and humidity. In stress conditions OME stability should improve under inclusion complex form with hydroxypropyl-b-cyclodextrin (HPbCD). Stability of OME, its physical mixture (PM) with HPbCD and OME:HPbCD inclusion complex was assessed during 60 days. The inclusion complexes were prepared by kneading and freezedrying techniques and characterized by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). A molecular modelling was also held to predict the most probable tridimensional conformation of inclusion complex OME:HPbCD. The inhibitory activity of free and complexed OME on selected enzymes, namely, papain (protease model of the proton pump) and acetylcholinesterase (enzyme present in cholinergic neurons and also involved in Alzheimer’s disease) was compared. The results obtained show that HPbCD do not protect against OME degradation, in any prepared powder, in the presence of light, heat and humidity. This may indicate that the reactive group of OME is not included in the HPbCD cavity. This fact is supported by molecular modelling data, which demonstrated that 2-pyridylmethyl group of OME is not included into the cyclodextrin cavity. In relation to enzymatic assays it was observed that free OME and OME in the binary systems showed identical inhibitory activity on papain and acethylcolinesterase, concluding that HPbCD do not affect OME activity on these two enzymes. Description: The original publication is available at www.springerlink.com. A publicação original está disponível em www.springerlink.com

2010-10-28T00:00:00Z Salústio, Paulo Marques, Helena Cabral Costa, Paulo Pinto, João http://hdl.handle.net/10451/3853 2011-08-05T17:01:07Z 2010-12-30T00:00:00Z

Title: Comparison of ibuprofen release from minitablets and capsules containing ibuprofen: β-Cyclodextrin complex Authors: Salústio, Paulo; Marques, Helena Cabral; Costa, Paulo; Pinto, João Abstract: Mixtures containing ibuprofen (IB) complexed with b-cyclodextrin (bCD) obtained by two complexation methods [suspension/solution (with water removed by air stream, spray- and freeze-drying) and kneading technique] were processed into pharmaceutical dosage forms (minitablets and capsules). Powders (IB, bCD and IBbCD) were characterized for moisture content, densities (true and bulk), angle of repose and Carr’s index, X-ray and NMR. From physical mixtures and IBbCD complexes without other excipients were prepared 2.5-mm-diameter minitablets and capsules. Minitablets were characterized for the energy of compaction, tensile strength, friability, density and IB release (at pH 1.0 and 7.2), whereby capsules were characterized for IB release. The results from the release of IB were analyzed using different parameters, namely, the similarity factor (f2), the dissolution efficiency (DE) and the amounts released at a certain time (30, 60 and 180 min) and compared statistically (a = 0.05). The release of IB from the minitablets showed no dependency on the amount of water used in the formation of the complexes. Differences were due to the compaction force used or the presence of a shell for the capsules. The differences observed were mostly due to the characteristics of the particles (dependent on the method considered on the formation of the complexes) and neither to the dosage form nor to the complex of the IB. Description: NOTICE: this is the author’s version of a work that was accepted for publication in European Journal of Pharmaceutics and Biopharmaceutics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Eur J Pharm Biopharm. 2011 May;78(1):58-66. Epub 2010 Dec 30.

2010-12-30T00:00:00Z