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In this study, we investigated the formation of a co-amorphous system of tranilast (TRL) and diphenhydramine hydrochloride (DPH), which are drugs used for treating allergies and inflammation. The crystallization from undercooled melts of the drugs and drug mixtures was evaluated by thermal analysis. Both drugs in the amorphous state underwent crystallization on heating, although the mixture remained in the amorphous state, indicating the formation of a co-amorphous system. The physicochemical properties of co-amorphous TRL-DPH prepared by the melting-cooling process were studied. The glass transition temperature of co-amorphous TRL-DPH deviated from the theoretical value. The enthalpy relaxation rate of the amorphous drugs, which reflected the molecular mobility, was reduced by the formation of a co-amorphous system. The intermolecular interactions between TRL and DPH in the co-amorphous system were measured by the change in the IR spectra. These results were consistent with the high physical stability. The co-amorphous sample remained in the amorphous state for over 30 days at 40°C, whereas the amorphous drugs showed rapid crystallization. Our findings demonstrate that TRL and DPH form a co-amorphous system, which dramatically decreases their crystallization without an excipient.

The results showed a relationship between stable co-amorphous formation and the physicochemical features of the components, which should inform efficient co-former selection to design stable co-amorphous formations.

Crocetin (CRT) has shown various neuroprotective effects such as antioxidant activities and the inhibition of amyloid β fibril formation, and thus is a potential therapeutic candidate for Alzheimer's disease (AD). However, poor water solubility and bioavailability are the major obstacles in formulation development and pharmaceutical applications of cRt. in this study, a novel water-soluble cRt-γcyclodextrin inclusion complex suitable for intravenous injection was developed. the inclusion complex was nontoxic to normal neuroblastoma cells (N2a cells and SH-SY5Y cells) and AD model cells (7PA2 cells). furthermore, it showed stronger ability to downregulate the expression of c-terminus fragments and level of amyloid β in 7PA2 cell line as compared to the CRT free drug. Both inclusion complex and CRT were able to prevent SH-SY5Y cell death from H 2 o 2-induced toxicity. the pharmacokinetics and biodistribution studies showed that cRt-γ-cyclodextrin inclusion complex significantly increased the bioavailability of cRt and facilitated cRt crossing the blood-brain barrier to enter the brain. this data shows a water-soluble γ-cyclodextrin inclusion complex helped to deliver cRt across the blood-brain barrier. this success should fuel further pharmaceutical research on cRt in the treatment for AD, and it should engender research on γ-cyclodextrin with other drugs that have so far not been explored. Alzheimer's disease (AD) is an irreversible neurodegenerative disease which cannot be cured by any therapeutic approaches up to now 1. As the number of AD patients increases, the need to develop safe, effective drugs for AD therapy becomes increasingly urgent. In traditional herbal medicine, several plants have been used to treat the symptoms of neurodegenerative diseases 2,3. Crocetin (CRT) is an active compound isolated from the fruits of gardenia (Gardenia jasminoides Ellis) and the stigmas of saffron (Crocus sativus L.) 4. Various pharmacological activities of CRT have been reported. CRT can inhibit amyloid β (Aβ) fibril formation, destabilize pre-formed Aβ fibrils and improve Aβ degradation in vitro 5,6. CRT can also reduce Aβ 1-42-induced neurotoxicity by attenuating oxidative stress in murine hippocampal cells 7. Furthermore, CRT can reduce the production of various neurotoxic molecules from neuron, such as lipopolysaccharide (LPS)-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and reactive oxygen species (ROS), which provided strong protection from neuronal cell death 8,9. Moreover, CRT has been proven to cross the blood-brain barrier (BBB) limitedly after administration 10. The mentioned properties of CRT indicate that it may be a potentially useful candidate for AD treatment. In terms of its chemical structure (Fig. 1A), CRT contains two carboxylic acid groups at each end of a polyene chain. However, CRT is insoluble in water in the physiological range (0.0056 g/L); it can only slightly dissolve in pyridine, dimethyl sulfoxide or aqueous alkali solutions at pH above 9 11. Poor solub...

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Eudragit E (EGE) is a basic polymer incorporating tertiary amino and ester groups. The role of the functional groups of EGE in the formation of solid dispersion (SD) with Naproxen (NAP) was investigated. The glass transition temperature (Tg) of EGE decreased with the plasticizing effect of NAP up to 20% weight ratio. Addition of NAP at over 30% induced a rise in Tg, with the maximum value being reached at 60% NAP. Further addition of NAP led to a rapid drop of the Tg. A dramatic difference of physical stability between the SDs including 60 and 70% NAP was confirmed. The SD including 70% NAP rapidly crystallized at 40 °C with 75% relative humidity, while the amorphous state could be maintained over 6 months in the SD with 60% NAP. The infrared and (13)C solid state-NMR spectra of the SDs suggested a formation of ionic interaction between the carboxylic acid of NAP and the amino group of EGE. The SD with 20% NAP raised the (13)C spin-lattice relaxation (T1) of the amino group, but it decreased with over 30% NAP. The change in the (13)C-T1 disappeared with 70% NAP. The (13)C-T1 of the ester group rose depending on the amount of NAP. From these findings, we concluded that the role as hydrogen acceptor shifted from the amine to the ester group with an increase in amount of NAP. Furthermore, the amino group of EGE did not contribute to the interaction at over 70% NAP. These phenomena could be strongly correlated with Tg and stability.

Stress thallium-201 myocardial distribution was quantitatively evaluated by emission transaxial tomography in 104 patients who underwent coronary arteriography. The initial uptake and percent washout of thallium were assessed by the circumferential profile curves of the three short-axis sections and one middle right anterior oblique long-axis section. This quantitative tomographic analysis showed abnormal distribution in all but two patients (98%) with coronary artery disease, whereas qualitative analysis showed abnormality in 76 of the patients (93%). Quantitative analysis showed better sensitivity (91%) for detecting involved coronary vessels than qualitative analysis (80%, p less than 0.01), especially in three vessel disease (82 versus 67%, p less than 0.05). For localization of individual vessel involvement, quantitative analysis showed high sensitivity (right coronary artery: 96%, left anterior descending artery: 90% and left circumflex artery: 88%) as compared with qualitative analysis (88, 83 and 63%, respectively, p less than 0.05), while similar specificity was observed (92% for quantitative and 93% for qualitative analyses). Furthermore, in the study of patients without infarction, myocardial segments supplied by coronary vessels with moderate stenosis (51 to 75%) revealed abnormality more often with quantitative (81%) than with qualitative (56%) analysis. Thus, quantitative analysis of stress thallium emission tomography provides improved sensitivity for the detection of diseased coronary vessels in patients with three vessel disease and those with moderate stenosis. It is a valuable technique for the evaluation of coronary artery disease.

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