Charge-assisted bond N+H mediates the gelation of amorphous lurasidone hydrochloride during dissolution

Publication date: 25 February 2017 Source:International Journal of Pharmaceutics, Volume 518, Issues 1–2 Author(s): Shuai Qian, Shanshan Wang, Zhen Li, Xiaojie Wang, Di Ma, Shujun Liang, Yuan Gao, Jianjun Zhang, Yuanfeng Wei Lurasidone hydrochloride (LH), the hydrochloride form of lurasidone with a charge-assisted bond N+ H, is an atypical antipsychotropic agent for the treatment of schizophrenia. As a BCS class II drug, LH has a low oral bioavailability mainly due to its poor water solubility and low dissolution. In order to improve its solubility, amorphization of LH was performed and characterized. Unexpectedly, the dissolution rate of amorphous LH was much lower than that of crystalline LH. In addition, the amorphous LH powders quickly aggregated when contacting the dissolution media (water, 37°C), and formed a sticky gel adhering on the paddle. The follow-up polarized light microscope, XRPD, DSC, and FTIR analysis found that amorphous LH transformed to crystalline LH during dissolution. On the other hand, no such gelation phenomenon of amorphous lurasidone was observed under the same dissolution condition. However, the gel would reform when dropping concentrated hydrochloric acid slowly into the bottom of the medium during the dissolution of amorphous lurasidone, and XRPD/DSC/FTIR results indicated that the regenerated gel was consisted of crystalline LH, suggesting that the charge-assisted bond N+ H in the structure of LH mediated the gel formation of amorpho...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research

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Authors: Bulbena-Cabre A, Bulbena A PMID: 30027877 [PubMed - in process]
Source: The British Journal of Psychiatry for Mental Science - Category: Psychiatry Tags: Br J Psychiatry Source Type: research
Publication date: Available online 21 July 2018Source: Journal of Psychiatric ResearchAuthor(s): Ragy R. Girgis, Anthony W. Zoghbi, Daniel C. Javitt, Jeffrey A. LiebermanAbstractSince the discovery of chlorpromazine in the 1950's, antipsychotic drugs have been the cornerstone of treatment of schizophrenia, and all attenuate dopamine transmission at the dopamine-2 receptor. Drug development for schizophrenia since that time has led to improvements in side effects and tolerability, and limited improvements in efficacy, with the exception of clozapine. However, the reasons for clozapine's greater efficacy remain unclear, desp...
Source: Journal of Psychiatric Research - Category: Psychiatry Source Type: research
Variation within voltage-gated calcium channel genes and antipsychotic treatment response in a South African first episode schizophrenia cohort, Published online: 22 July 2018; doi:10.1038/s41397-018-0033-5Variation within voltage-gated calcium channel genes and antipsychotic treatment response in a South African first episode schizophrenia cohort
Source: The Pharmacogenomics Journal - Category: Drugs & Pharmacology Authors: Source Type: research
Theory of Mind (ToM) refers to the cognitive ability of inferring intentions, and beliefs that oneself and others hold (Premack,  1978). ToM deficits have been suggested as a key cognitive aspect of schizophrenia (Frith, 1992). Actually, a large body of research confirms that ToM is disrupted in patients with schizophrenia (Brune, 2005). Moreover, these deficits seem to be independent of other deficits in executive functio ning or general neurocognitive impairments (van Hooren et al., 2008).
Source: Psychiatry Research - Category: Psychiatry Authors: Source Type: research
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Source: Iranian Journal of Pharmaceutical Research - Category: Drugs & Pharmacology Source Type: research
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Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
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Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
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Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
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Source: European Psychiatry - Category: Psychiatry Source Type: research
ConclusionsEarly detection and early intervention programs, timely intervention, and relapse prevention are essential for effective management of schizophrenia. It requires a paradigm shift from symptom control, achieving and maintaining remission, to the emphasis on recovery. Since the current services are not able to accomplish this goal, changes in mental health policies are needed.
Source: European Psychiatry - Category: Psychiatry Source Type: research
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