Kristalne modifikacije i profil oslobađanja piroksikama

Piroxicam is a nonsteroidal anti-inflammatory drug with low aqueous solubility which exhibits polymorphism. The present study was carried out to develop polymorphs of piroxicam with enhanced solubility and dissolution rate by the crystal modification technique using different solvent mixtures prepared with PEG 4000 and PVP K30. Physicochemical characteristics of the modified crystal forms of piroxicam were investigated by X-ray powder diffractometry, FT-IR spectrophotometry and differential scanning calorimetry. Dissolution and solubility profiles of each modified crystal form were studied and compared with pure piroxicam. Solvent evaporation method (method I) produced bothneedle and cubic shaped crystals. Slow crystallization from ethanol with addition of PEG 4000 or PVP K30 at room temperature (method II) produced cubic crystal forms. Needle forms produced by method I improved dissolution but not solubility. Cubic crystals produced by method I had a dissolution profile similar to that of untreated piroxicam but showed better solubility than untreated piroxicam. Cubic shaped crystals produced by method II showed improved dissolution, without a significant change in solubility. Based on the XRPD results, modified piroxicam crystals obtained by method I from acetone/benzene were cube shaped, which correlates well with the FTIR spectrum; modified needle forms obtained from ethanol/methanol and ethanol/acetone showed a slight shift of FTIR peak that may be attributed to differences in the internal structure or conformation.Piroksikam je nesteroidni protuupalni lijek male topljivosti u vodi koji ima svojstvo polimorfije. Cilj rada bio je priprema polimorfa piroksikama povećane topljivosti i brzine oslobađanja koristeći smjese različitih otapala i PEG 4000, odnosno PVP K30. Fizikokemijska svojstva modificiranih kristalnih oblika piroksikama ispitivana su difrakcijom X-zraka na praškastom uzorku FT-IR spektrofotometrijom i diferencijalnom pretražnom kalorimetrijom. Profili oslobađanja i topljivosti modificiranih kristalnih oblika proučavani su i uspoređivani sa čistim piroksikamom. Metodom uparavanja otapala (metoda I) dobiveni su igličasti i kubični kristali. Polaganom kristalizacijom iz etanola uz dodatak PEG 4000 ili PVP K30 na sobnoj temperaturi (metoda II) dobiveni su kubični kristali. Igličasti kristali dobiveni metodom I poboljšali su oslobađanje, ali ne i topljivost. Kubični kristali dobiveni metodom I imali su poboljšanu topljivost, ali sličan profil oslobađanja kao i netretirani piroksikam. Kubični kristali dobiveni metodom II imali su poboljšani profil oslobađanja, bez značajne promjene u topljivosti. Na temelju XRPD rezultata, modificirani kristali piroksikama dobiveni metodom I iz smjese acetona i benzena bili su kubični, što dobro korelira s FTIR spektrom; modificirani igličasti kristali dobiveni iz smjese etanol/metanol i etanol/aceton imali su lagani pomak FTIR signala što bi se moglo pripisati razlikama u internoj strukturi ili konformacijama

Molecular modeling of temperature dependence of solubility parameters for amorphous polymers

A molecular modeling strategy is proposed to describe the temperature (T) dependence of solubility parameter (δ) for the amorphous polymers which exhibit glass-rubber transition behavior. The commercial forcefield “COMPASS” is used to support the atomistic simulations of the polymer. The temperature dependence behavior of δ for the polymer is modeled by running molecular dynamics (MD) simulation at temperatures ranging from 250 up to 650 K. Comparing the MD predicted δ value at 298 K and the glass transition temperature (Tg) of the polymer determined from δ–T curve with the experimental value confirm the accuracy of our method. The MD modeled relationship between δ and T agrees well with the previous theoretical works. We also observe the specific volume (v), cohesive energy (Ucoh), cohesive energy density (ECED) and δ shows a similar temperature dependence characteristics and a drastic change around the Tg. Meanwhile, the applications of δ and its temperature dependence property are addressed and discussed

Molecular modeling simulation and experimental measurements to characterize chitosan and poly(vinyl pyrrolidone) blend interactions

หนึ่งอาจารย์หนึ่งผลงาน ประจำปี 255

Layer-by-layer gelatin/chitosan polyelectrolyte coated nanoparticles on Ti implants for prevention of implant-associated infections

Gelatin nanoparticles (Gb-NP) and layer-by-layer (LBL) coated NPs were developed to modify a Ti substrate surface to prevent implant-associated infections. Vancomycin (Van) was loaded into these materials to obtain GbV-NP and LBL-GbV-NP. The size of the GbV-NP (277.4±1.4 nm) was smaller than that of LBL-GbV-NP (710.2±4.6 nm) but both had a spherical shape. These coated materials showed no cytotoxicity and facilitated better cell proliferation by osteoblast-like cells compared to the bare Ti. This was probably due to the roughness of the coated NP that enhanced cell attachement to the surface. Both coated materials showed antibacterial activity against S. aureus. The release of Van from GbV-NP was higher from LBL-GbV-NP and this corresponded to their antibacterial activity. Furthermore the release profile of Van showed a sustained release. Thus both materials should be able to prolong the protection of implant-associated infections to the bone

Characterization of Cimetidine–Piroxicam Coprecipitate Interaction Using Experimental Studies and Molecular Dynamic Simulations

The crystalline states of cimetidine and piroxicam, when coprecipitated from solvents containing 1:1 mole ratio, were transformed to amorphous states as observed using powder X-ray diffraction (PXRD). Amorphous forms of drugs generally exhibit higher water solubility than crystalline forms. It is therefore interesting to investigate the interactions that cause the transformation of both the crystalline drugs. Intermolecular interactions between the drugs were determined using Fourier-transform infrared spectroscopy (FTIR) and solid-state 13C CP/MAS NMR. Molecular dynamic (MD) simulation was performed for the first time for this type of study to indicate the specific groups involved in the interactions based on radial distribution function (RDF) analyses. RDF is a useful tool to describe the average density of atoms at a distance from a specified atom. FTIR spectra revealed a shift of the C≡N stretching band of cimetidine. The 13C CP/MAS NMR spectra indicated downfield shifts of C11, C15 and C7 of piroxicam. RDF analyses indicated that intermolecular interactions occurred between the amide oxygen atom as well as the pyridyl nitrogen of piroxicam and H-N3 of cimetidine. The hydrogen atom (O–H) at C7 interacts with the N1 of cimetidine. Since the MD simulation results are consistent with, and complementary to the experimental analyses, such simulations could provide a novel strategy for investigating specific interacting groups of drugs in coprecipitates, or in amorphous mixtures