Tuning Mechanical Properties of Pharmaceutical Crystals with Multicomponent Crystals: Voriconazole as a Case Study

Crystals of voriconazole, an antifungal drug, are soft in nature, and this is disadvantageous during compaction studies where pressure is applied on the solid. Crystal engineering is used to make cocrystals and salts with modified mechanical properties (e.g., hardness). Cocrystals with biologically safe coformers such as fumaric acid, 4-hydroxybenzoic acid, and 4-aminobenzoic acid and salts with hydrochloric acid and oxalic acid are prepared through solvent assisted grinding. The presence (salt) or absence (cocrystal) of proton transfer in these multicomponent crystals is unambiguously confirmed with single crystal X-ray diffraction. All the cocrystals have 1:1 stoichiometry, whereas salts exhibit variable stoichiometries such as HCl salt (1:2) and oxalate salts (1:1.5 and 1:1). The nanoindentation technique was applied on single crystals of the salts and cocrystals. The salts exhibit better hardness than the drug and cocrystals in the order salts drug cocrystals. The molecular origin of this mechanical modulation is explained on the basis of slip planes in the crystal structure and relative orientations of the molecules with respect to the nanoindentation direction. The hydrochloride salt is the hardest solid in this family. This may be useful for tableting of the drug during formulation and in drug development.

Fiscal Policy and Economic Stability: Does PIGS stand for Procyclicality In Government Spending?

The Financial Crisis has hit particularly hard countries like Ireland or Spain. Procyclical fiscal policy has contributed to a boom-bust cycle that undermined fiscal positions and deepened current account deficits during the boom. We set up an RBC model of a small open economy, following Mendoza (1991), and introduce the effect of fiscal policy decisions that change over the cycle. We calibrate the model on data for Ireland, and simulate the effect of different spending policies in response to supply shocks. Procyclical fiscal policy distorts intertemporal allocation decisions. Temporary spending boosts in booms spur investment, and hence the need for external finance, and so generates very volatile cycles in investment and the current account. This economic instability is also harmful for the steady state level of output. Our model is able to replicate the relation between the degree of cyclicality of fiscal policy, and the volatility of consumption, investment and the current account observed in OECD countries.

On the Informational Role of Term Structure in the U.S. Monetary Policy Rule

This paper uses a structural approach based on the indirect inference principle to estimate a standard version of the new Keynesian monetary (NKM) model augmented with term structure using both revised and real-time data. The estimation results show that the term spread and policy inertia are both important determinants of the U.S. estimated monetary policy rule whereas the persistence of shocks plays a small but significant role when revised and real-time data of output and inflation are both considered. More importantly, the relative importance of term spread and persistent shocks in the policy rule and the shock transmission mechanism drastically change when it is taken into account that real-time data are not well behaved.

The Importance of Stock Market Returns in Estimated Monetary Policy Rules: a Structural Approach

This paper estimates a standard version of the New Keynesian Monetary (NKM) model augmented with financial variables in order to analyze the relative importance of stock market returns and term spread in the estimated U.S. monetary policy rule. The estimation procedure implemented is a classical structural method based on the indirect inference principle. The empirical results show that the Fed seems to respond to the macroeconomic outlook and to the stock market return but does not seem to respond to the term spread. Moreover, policy inertia and persistent policy shocks are also significant features of the estimated policy rule.

Term Structure and the Estimated Monetary Policy Rule in the Eurozone

Published as an article in: Spanish Economic Review, 2008, vol. 10, issue 4, pages 251-277.