Utjecaj superdezintegratora na oslobađanje efavirenca iz tableta

Efavirenz (EFV) tablets of different doses were prepared by a wet granulation process using different superdisintegrants such as crosscarmellose sodium (CCS), sodium starch glycollate (SSG) and crosspovidone (CP) to evaluate the role of different disintegrants on the in vitro release of EFV. Further, the mode of addition of disintegrants on EFV dissolution from tablets containing 600 mg of the drug was evaluated by incorporating the disintegrant extragranularly (EG), intragranularly (IG) or distributing them equally (IG and EG). In vitro dissolution of the prepared tablets was conducted using the recommended medium and a dissolution medium developed in-house, which had the propensity to discriminate between the formulations. The t50 and t80 values were indicative of the fact that drug release was faster from tablet formulations containing CP. CP was able to release the drug faster than the other two disintegrants in both dissolution media and the drug release was unaffected by the mode of CP addition.U radu je opisana priprava tableta s različitim dozama efavirenca (EFV) metodom vlažne granulacije. Za tabletiranje korišteni su različiti superdezintegratori, poput natrijeve kroskarameloze (CCS), natrijeva škrobnog glikolata (SSG) i krospovidona (CP), kako bi se procijenio utjecaj vrste i načina dodavanja dezintegratora na oslobađanje EFV in vitro. U tu svrhu pripravljene su tablete sa 600 mg EFV, a dezintegrator je dodavan ekstragranularno (EG), intragranularno (IG) ili je bio podjednako raspršen (IG i EG). In vitro oslobađanje praćeno je u preporučenom mediju i mediju izrađenom u našem laboratoriju kako bi se uočila razlika između formulacija. Vrijednosti t50 i t80 ukazuju na to da je oslobađanje lijeka brže iz formulacija koje sadrže CP u oba medija. Način dodavanja CP nema utjecaj na oslobađanje lijeka, osim za CCS, gdje se ekstragranularno dodavanje pokazalo povoljnijim

Enhanced pharmacological efficacy of sumatriptan due to modification of its physicochemical properties by inclusion in selected cyclodextrins

The study focused on the pharmacological action of sumatriptan, in particular its antiallodynic and antihyperalgesic properties, as an effect of cyclodextrinic inclusion of sumatriptan, resulting in changes of its physicochemical qualities such as dissolution and permeability through artificial biological membranes, which had previously been examined in vitro in a gastro-intestinal model. The inclusion of sumatriptan into β-cyclodextrin and 2-hydroxylpropylo-β-cyclodextrin by kneading was confirmed with the use of spectral (fourier-transform infrared spectroscopy (FT-IR); solid state nuclear magnetic resonance spectroscopy with magic angle spinning condition, 1H and 13C MAS NMR) and thermal (differential scanning calorimetry (DSC)) methods. A precise indication of the domains of sumatriptan responsible for its interaction with cyclodextrin cavities was possible due to a theoretical approach to the analysis of experimental spectra. A high-performance liquid chromatography with a diode-array detector method (HPLC-DAD) was employed to determine changes in the concentration of sumatriptan during dissolution and permeability experiments. The inclusion of sumatriptan in complex with cyclodextrins was found to significantly modify its dissolution profiles by increasing the concentration of sumatriptan in complexed form in an acceptor solution compared to in its free form. Following complexation, sumatriptan manifested an enhanced ability to permeate through artificial biological membranes in a gastro-intestinal model for both cyclodextrins at all pH values. As a consequence of the greater permeability of sumatriptan and its increased dissolution from the complexes, an improved pharmacological response was observed when cyclodextrin complexes were applied

Glass transitions in binary drug + polymer systems

To evaluate miscibility, glass transition temperatures Tg have been determined for two binary polymer (Plasdone S-630 copovidone or Eudragit® E) + drug systems as a function of composition. Each polymer serves for encapsulation of the anti-HIV drug Efavirenz. In both systems the Tg vs. drug concentration diagrams are s-shaped. Tgs of Efavirenz + Plasdone mixtures with drug mass fraction below φdrug = 0.6 are above linear values. This implies enhanced thermal and mechanical stability-an advantage for the drug encapsulation. In the other system, a strong negative deviation of Tgs is observed over the entire compositional range and explained by positive excess mixing volumes. Several equations are used to represent Tg vs. composition diagrams, but only one (Brostow et al. Mater Lett 2008; 62:3152) provides reliable results. © 2009 Elsevier B.V. All rights reserved

Encapsulation of hydrophobic drugs in a copolymer: Glass transition behavior and miscibility evaluation

The knowledge of glass transition temperatures Tg in drug + polymer systems is indispensable for drug encapsulation. Tg values as a function of composition make possible the determination whether a given polymer is miscible or compatible with the drug and whether the polymer will provide release of the drug into organism within an acceptable rate range. We have used differential scanning calorimetry and Fourier-transform infrared spectroscopy to evaluate miscibility in solid dispersions of the drugs carvedilol, itraconazole, nevirapine, and nimodipine in the pharmaceutical grade copolymer poly(vinyl pyrrolidone-co-vinyl acetate) (PLS-630 Copovidone). Successful drug encapsulation is discussed in terms of thermophysical behavior (suppression of crystallization, negative excess volumes of mixing) and intermolecular interactions (concentrations of proton donating/accepting groups) in drug + polymer systems. Several equations were applied to the complex s-shaped Tg(φ) patterns obtained (φ being the mass fraction of the drug). The best agreement of calculations with experiment is achieved using a recently proposed three-parameter equation, symmetric with respect to the equal concentration of both components. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers