chemistry journal of moldova

Ion Dranca/Chem.J. Mold. 2008, 3 (1), 31-43are inherently unstable because of a strong thermodynamic drive toward crystallization. A great deal of studies hasbeen concerned with evaluating the physical stability of amorphous drugs. Most of these studies have been focusedon the dynamics of the glass transition (-relaxation), because this is the process that on its heating transforms anamorphous system from a low- to high-mobility state, in which crystallization occurs very quickly. It is known thatthe molecular mobility associated with the -relaxation fades away rapidly as the temperature drops below the glasstransition temperature, T g . Nevertheless, slow crystallization of indomethacin has been reported by several workers[39, 40] at temperature as low as 20 o C, which is about 25 o C below the respective T g value. On the other hand,relaxation in amorphous indomethacin is still detectable as much as 47 o C below T g [41]. It seems to be generallythought that at temperature 50 o C below T g , the molecular mobility should be too negligible to cause any significantrelaxation and, therefore, crystallization. This is certainly true for the -relaxation that requires a cooperative motionof multiple molecules and therefore has a huge energy to it. However, local noncooperative motion has a significantlysmaller energy barrier and continues to occur at lower temperatures, giving rise to the -process [46]. Although the-relaxations (Fig. 1) had been well known for polymers, Johari and Goldstein [42] discovered similar processes insimple inorganic glasses, and suggested these to be universal feature of the glassy state.1.3 Glucose (Gl) and Maltitol (Mt). Sugar and sugar alcohols find a wide application in various pharmaceuticalsystems as sweeteners and/or binding matrices for drug components. As such they are frequently used in the glassy state,which is thermodynamically unstable and unavoidably tends to relax toward the liquid state [43]. Understanding thedynamics of this process is of a great practical importance for designing physically stable formulations of amorphousdrugs.In this work, we apply DSC to measure the -relaxation in a PS-clay system, in virgin PS, in amorphousindomethacin, and also in amorphous glucose and maltitol. The objective of this study is to obtain comparative informationon the relaxation dynamics of these systems by estimating the effective activation energies of the relaxation as well asthe sizes of cooperatively rearranging regions at the glass transition. This paper is intended to initiate systematic kineticstudies of polymer nanocomposites and pharmaceutic materials, therefore, to fill the presently existing void in theunderstanding of the thermal behavior of these exciting materials.Experimental SectionA sample of the PS-clay composite was provided by Dr. Xiaowu Fan (Northwestern University). The compositewas prepared by intercalating a monocationic free radical initiator into montmorillonite clay and the subsequentsolution surface-initiated polymerization (SIP), where the chain growth was initiated in situ from clay surfaces. Themontmorillonite clay was Cloisite ® Na + (Southern Clay Product Inc.) with the cation exchange capacity 92 mequiv per100g and the specific surface area 750 m 2 g -1 . The initiator was an azobisisobutyronitrile (AIBN)-analogue moleculewith a quaternized amine group at one end. The intercalation process was realized by cation exchange reaction in whichthe cationic end of the initiator was ionically attached to the negatively charged clay surfaces. The details regarding thepreparation and characterization of the intercalated clay can be found elsewhere [44]. The subsequent SIP was performedin THF solvent with styrene as the monomer, resulting in a PS-clay nanocomposite by the in situ polymerization. Detailsof the initiator synthesis, the SIP process and product analysis can be found in previous publication, which shows thatthis free radical SIP strategy can achieve exfoliated PS-clay nanocomposites of high clay loading. According to ourpervious TGA [45] measurements the resulting composite contains about 1% of clay by weight. The molecular weight(~90,000) and polydispersity (~2.3) of the product were measured by size exclusion chromatography (SEC) usingPS standards. The obtained material will be referred to as nPS90. For comparison purposes, we have used radicallypolymerized PS that was purchased from Alfa Aesar and used as received. Its Mw value is 100,000 (polydispersity isaround 2.1) and it will be referred to as PS100.The -relaxation measurements were performed on ~10 mg samples placed in 40L Al pans. The glass transitionwas measured by heating a sample ~40°C above its glass transition temperature and holding it at this temperature for 10min to erase thermal history. The samples were then cooled down to ~40°C below the glass transition temperature at therates form 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5 and 25 °C min -1 . Immediately after completion of the cooling segment, thesamples were heated at a rate whose absolute value was equal to the rate of preceding cooling. TGA data [45] indicatethat no detectable degradation of PS100 and nPS90 occurs in air below 240°C.Indomethacin(1-(p-chlorobenzoil)-5-methoxy-2-methylindole-3-acetic acid) was obtained from MP Biomedicals,LLC (catalogue number 190217, lot number 9331E), with a melting point at 160oC obtained by DSC, and it was usedwithout further purification.The -relaxation measurements were performed on ~10.0 mg samples placed in 40L Al sealed pans withoutholes. TGA data [46] indicate that no detectable degradation of Indomethacin occurs in air atmosphere below 180°C.The glass transition was measured by heating a sample ~40°C above its glass transition temperature (90 o C) and holdingit at this temperature for 10 min to erase thermal history. The samples were then cooled down to ~40°C below the glasstransition temperature (-10 o C) at the rates form (10, 15, 20, 25 and 30°C min -1 ). Immediately after completion of the33