Stability and enzymatic studies with omeprazole: hydroxypropyl-β-cyclodextrin

The original publication is available at www.springerlink.com. A publicação original está disponível em www.springerlink.comOmeprazole (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

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

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