Amisulpride Research Articles

Microenvironmental pH-modified Amisulpride-Labrasol matrix tablets: development, optimization and in vivo pharmacokinetic study.

Amisulpride (AMS) is atypical antipsychotic with a weak basic nature (pKa 9.37), which results in low solubility in the high pH of the intestine. It is also recognized as a substrate of P-glycoprotein efflux pump. Both factors lead to its low oral bioavailability (48%). The daily dose of AMS is between 200 and 1200mg to be taken in divided doses which compromise patient compliance. Therefore, controlled release formulation of AMS is of clinical significance. AMS was formulated into matrix tablets containing Labrasol, P-glycoprotein efflux inhibitor, and a penetration enhancer, using direct compression technique. The tablets were prepared according to 21·41 factorial design using two polymers, namely, HPMC and Carbopol 934 at four concentrations (20%, 30%, 40%, 50%). Percentage AMS released after 2h (Q2hr%) and 8h (Q8hr%) were chosen as dependent variables. Two acidic pH modifiers (fumaric acid and tartaric acid) at two levels (15% and 30%) were incorporated in the tablet according to 22 factorial design. All formulae with acidic pH modifier had similarity factor (f2) ≥ 50 proving the pH independent release of AMS. The pharmacokinetic study in rabbits revealed 30% enhancement of the oral absorption AMS imparted by the pH-modified matrix tablet containing Labrasol. Graphical abstract.

C-Fos and FosB/ΔFosB colocalizations in selected forebrain structures after olanzapine, amisulpride, aripiprazole, and quetiapine single administration in rats preconditioned by two different mild stressors sequences.

Olanzapine (OLA), amisulpride (AMI), aripiprazole (ARI), and quetiapine (QUE) belong to antipsychotics, which administration represents still most reliable way for the treatment of schizophrenic and bipolar disorders. The intention of the present study was to explore whether the acute administration of a particular antipsychotic, indicated by the presence of c-Fos, will: a) stimulate neurons already activated by a long lasting homogeneous or heterogeneous stress preconditioning, indicated by the FosB/ΔFosB (ΔFosB) expression, or b) have a stimulatory effect only on a not activated, so called silent neurons. The pattern of ΔFosB and c-Fos spatial relationship was investigated in three forebrain structures, including the septal ventrolateral nucleus (seVL), the striatal dorsolateral area (stDL), and the shell of the nucleus accumbens (shell). The rats were divided into 10 groups and exposed to two types of stressors. Half of them was exposed to a sequence of homogeneous stressor - handling (HDL) and the other half to a heterogeneous stressor (CMS) daily for 20 days. CMS consisted of five types of stressors: crowding, air-puff, wet bedding, predator stress, and forced swimming applied in an unexpected order. On the 21st day of the experiment, the rats were free of the stress exposure and on the 22nd day, both groups of animals receive a single intraperitoneal injection of vehicle (4% DMSO in saline, 0.1 ml/100 g) or OLA (5 mg/kg), AMI (20 mg/kg), ARI (10 mg/kg), and QUE (15 mg/kg). 90 min after the drugs administration the animals were transcardially perfused, brains removed, cut into 30 µm thick coronal sections, and double stained: first with ΔFosB antibody linked with Alexa488 fluorescent dye and second with c-Fos antibody linked to Alexa596 one. Quantitative evaluation of ΔFosB and c-Fos colocalizations was performed on fluorescence photomicrographs transformed into a final picture containing only yellow, green, and red colored circles. The data of this investigation demonstrate that ΔFosB and c-Fos colocalizations occurred in each of the three areas investigated, i.e. seVL, stDL, and shell ones, in both HDL as well as CMS preconditioned rats. The levels of ΔFosB and c-Fos colocalizations varied in the individual forebrain areas studied. From the total 22 areas measured, level of c-Fos colocalization prevailed over ΔFosB in 18 ones. However, neither c-Fos nor ΔFosB reached 100% level of colocalization in any of the forebrain areas investigated. The present findings indicate that ΔFosB and c-Fos colocalizations occurred in each of the three areas investigated, i.e. seVL, stDL, and shell, in both HDL and CMS preconditioned rats, whereas the parallel occurrence of free c-Fos as well as c-Fos colocalized with ΔFosB might speak out for a possible involvement of the c-Fos activated by antipsychotics applied in dual, i.e. short- and long-lasting, functions.

Conjugation of Amisulpride, an Anti-Psychotic Agent, with 5-Aminosalicylic Acid via an Azo Bond Yields an Orally Active Mutual Prodrug against Rat Colitis.

Amisulpride (ASP), an anti-psychotic agent, is a pharmacologically equivalent to sulpiride (SP). Because SP demonstrates anti-ulcer and anti-colitic activities, ASP with an aniline moiety was azo-coupled to salicylic acid to generate 5-(aminoethanoylsulfamoyl)-N-[(1-ethylpyrrolidin-2-yl)methyl]-2-methoxybenzamide (ASP-azo-ASA), with the expectation that it would act as a colon-specific mutual prodrug against colitis. Following a 24 h incubation, approximately 80% of ASP-azo-ASA was cleaved to form ASP and 5-aminosalicylic acid (5-ASA) in the cecal contents, whereas it remained stable in the small intestinal contents. Oral gavage of ASP-azo-ASA (oral ASP-azo-ASA) delivered 5-ASA to the cecum to levels comparable with those observed for sulfasalazine (SSZ; clinical colon-specific prodrug of 5-ASA) and without detectable concentrations of ASP in the blood, indicating efficient colonic delivery. Oral ASP-azo-ASA ameliorated 2, 4-dinitrobenzenesulfonic acid hydrate (DNBS)-induced colitis in rats more effectively than oral SSZ. Additionally, oral ASP-azo-ASA lowered the levels of inflammatory mediators in the inflamed distal colon more effectively than oral SSZ. Combined treatment with 5-ASA and ASP via the rectal route more effectively reversed colonic damage and inflammation than treatment with 5-ASA or ASP alone, confirming the mutual anti-colitic actions of 5-ASA and ASP. In conclusion, ASP-azo-ASA is an orally active mutual prodrug against rat colitis with limited systemic absorption of ASP.

Amisulpride as an Augmentation Agent in Treatment Resistant Depression: A Case Series and Review of the Literature.

Amisulpride (AMS) in low dosage has been used effectively for treatment of dysthymia. Yet there is a dearth of reports on its use as an augmentation agent in therapy-resistant depression. We deal with this issue presenting case reports and a review of the literature. The addition of 50 mg amisulpride (AMS) to antidepressant therapy in seven patients with depression at different stages of treatment resistance, one of them a case of recurrent brief depression, is described in this report. Augmentation with AMS led to a profound improvement in psychopathology in most patients. The only side effects were elevation of prolactin levels and occasional weight gain. In most cases, improvement occurred early, after only 1-2 weeks of treatment. In some patients, reduction or cessation of AMS led to an immediate and intense recurrence of depressive symptoms that resembled a withdrawal syndrome. Further investigations into the clinical utility and the mode of action of AMS as an augmentation agent are warranted.

Spatial relationship between the c-Fos distribution and enkephalinergic, substance P, and tyrosine hydroxylase innervation fields after acute treatment with neuroleptics olanzapine, amisulpride, quetiapine, and aripiprazole in the rat septum.

The aim of the present study was to demonstrate the spatial relationship between the c-Fos immunoreactive cells elicited by an acute treatment with neuroleptics including amisulpride (AMI), olanzapine (OLA), quetiapine (QUE), and aripiprazole (ARI) and enkephalinergic (ENK), substance P (SP), and tyrosine hydroxylase (TH) innervation fields in the rat septum. Male Sprague Dawley rats received a single injection of OLA (5 mg), ARI (10 mg), AMI (20 mg), QUE (15 mg/kg/b.w.). Ninety min after antipsychotics administration, the animals were transcardially perfused with a fixative and the brains cryocut into serial coronal sections of 35 µm thickness. The sections were processed for c-Fos staining using an avidin-biotin-peroxidase complex and visualized by nickel intensified diaminobenzidine to reach black endproduct. Afterwards, the sections were exposed to ENK, SP, and TH antibodies and the reaction product visualized by biotin-labeled fluorescent AlexaFluor 564 dye. The data were evaluated from the sections either simultaneously illuminated with fluorescent and transmission microscope beams or after merging the separately illuminated sections in the Adobe Photoshop 7.0 software. ENK, SP, and TH displayed characteristic spatial images formed by a dense accumulation of immunoreactive fibers and terminals on the both sides of the septum. A dense plexus of axons formed by ENK and SP immunopositive terminals were situated predominantly in the lateral, while TH ones more medial portion of the septum. QUE and AMI activated distinct amount of c-Fos expression in cells located within the SP-immunoreactive principal innervation field. The OLA effect on the c-Fos expression was very pronounced in the ventral TH-labeled principal innervation field including the space between the ENK field ventral portion and the dorsal margin of the accumbens nucleus shell. Generally, the occurrence of c-Fos cells in the ENK-immunoreactive principal innervation field, in comparison with the surrounding septal area, was less abundant after all of the four antipsychotics treatments. The data of the present study indicate that ENK, SP, and TH innervation fields may influence separate populations of septal cells activated by AMI, OLA, QUE, and ARI and that each of these region-differently innervated cells may be associated with the functional heterogeneity of the individual lateral septal nuclei.

Anodic Voltammetric Determination of an Atypical Antipsychotic Drug Amisulphide in Pharmaceutical Dosage Forms Using Electrochemical fsDNA Biosensor

In this study, a new biosensor for amisulpride (ASP) determination is defined. The interaction between ASP and fish sperm double-stranded DNA (FSdsDNA) was examined by differential pulse voltammetry (DPV) method utilizing FSdsDNA modified pencil graphite electrode (PGE). Sensitive and reliable ASP determination and detection was performed in pH 4.80 acetate buffer (20% ethanol) before and after the interaction of ASP and FSdsDNA, acting by the change in guanine oxidation signals from the electro-active bases of FSdsDNA. In addition, analytical method validity tests were examined in this study. This modified electrode have used in 1–10 μg/mL determination interval for the quantitative determination of ASP in pharmaceutical forms and the limit of detection (LOD) has been found as 0.46 μg/mL. Also, the binding constants (Kb) of the ASP with FSdsDNA has also been calculated both UV-Vis and DPV techniques.

Development of two spectrophotometric methods for quantification of certain anti-depressant drug in pure, pharmaceutical formulation and application to content uniformity testing

Two accurate, rapid, simple, robust and extraction-free spectrophotometric techniques were created for assay of Amisulpride (AMS) in pure and tablet preparation. The described methods have been established on the reaction of methanolic solution of AMS with 4-(dimethylamino) benzaldehyde in acidic medium which give yellow product that can be determined at λmax = 400 nm (method-I) and the reaction AMS with tetrachloro-1, 4-benzoquinone (p-Ch) which yields intense blue to purple colored charge transfer complex that can be determined at λmax = 559 nm (method-II). The prescribed assay obeys Beer's law within the range from 20 to 200 and 50–400 micrograms per milliliter for method-I & method-II orderly. Detection limits have been 4.4 & 10.6 μg/mL while quantitation limits have been 13.2 & 32.0 micrograms per milliliter for method-I & method-II orderly. Developed methods were validated according to guidelines of International conference on Harmonization for the detection of cited drug in pure, pharmaceutical preparations and content uniformity testing.

C-Fos expression response to olanzapine, amisulpride, aripiprazole, and quetiapine single administration in the rat forebrain: Effect of a mild stress preconditioning

Antipsychotics have been shown to stimulate different forebrain areas, whereas some of them are sensitive to stress. In the present study, effect of a single administration of olanzapine (OLA), amisulpride (AMI), aripiprazole (ARI), and quetiapine (QUE) on the activity of cells in the striatal dorsolateral (stDL) area, the periventricular zone (peVZ), the septal ventrolateral (seVL) nucleus, and the accumbens nucleus shell (shACC) and core (coACC) was investigated in male rats preconditioned with a mild stress complex (CMS) for 20 days. The objective of the study was to extend the anatomical-functional knowledge on the mechanism of selected antipsychotics with the goals: 1) to analyze the ability of the selected antipsychotics to induce c-Fos protein expression in the above mentioned forebrain structures and to map the pattern of their topography and 2) to find out whether longer-lasting mild stress preconditioning may modify the impact of the selected antipsychotics on the activity of cells in the forebrain areas in adult rats. Ten groups of rats were used. CMS complex contained five stressors: cage crowding, air-puff noising, wet bedding, predator stress, and forced swimming. AMI (20 mg/kg), OLA (5 mg/kg), QUE (15 mg/kg), and ARI (10 mg/kg/b.w.) were administered intraperitoneally and 90 min later the animals transcardially perfused by fixative. c-Fos was visualized by ABC complex. In unstressed animals, OLA and ARI elevated c-Fos expression in all areas studied, AMI and QUE in all areas except stDL, seVL and coACC, shACC FL-2 (shACC posterior level), respectively. CMS potentiated the effect of AMI in coACC, and QUE in shACC FL-2 and suppressed the effect of AMI in peVZ, and ARI in peVZ and seVL. The present data provide new insights into activity of cells in response to CMS challenge, which might be helpful in understanding the diverse clinical effects of atypical antipsychotics.

Enhanced Oral Absorption of Amisulpride Via a Nanostructured Lipid Carrier-Based Capsules: Development, Optimization Applying the Desirability Function Approach and In Vivo Pharmacokinetic Study.

Amisulpride (AMS), a second generation antipsychotic, suffers from low oral bioavailability (48%). This might be due to its pH-dependent solubility or being a substrate of P-glycoprotein efflux pump. Nanostructured lipid carriers (NLCs) were proposed in this study to enhance the oral absorption of AMS. AMS-NLCs were prepared by solvent evaporation technique according to (21.41.31) factorial design, whereas the type of solid lipid (tripalmitin or Gelucire® 43/1), lipid to drug ratio (7:1, 10:1, or 13:1) and type of external suspending medium (double distilled water, 0.5% TSP pH 12, 1% HPMC or 2.5% glycerin) were the independent variables. The average entrapment efficiency, particle size, polydispersity index, and zeta potential of the prepared formulations ranged from 29.01 to 69.06%, 184.9 to 708.75nm, 0.21 to 0.59, and - 21 to - 33.55mV, respectively. AMS-NLCs were optimized according to the desirability function to maximize the entrapment efficiency and minimize the particle size. Formulae G12, G10, and G7 with the highest desirability values of 0.915, 0.84, and 0.768, respectively, were chosen for further investigations. Novel AMS-NLCs capsules were prepared from the lyophilized formulations (TG7 and MG10) to enhance stability and increase patient compliance. The capsules were evaluated in terms of weight variation, content uniformity, and in vitro release pattern. The pharmacokinetics of AMS-NLCs capsules (formula TG7) were tested in rabbits compared to the commercial Amipride® tablets. The relative bioavailability of AMS-NLCs capsules was found to be 252.78%. In conclusion, the NLC-based capsules show potential to improve the oral bioavailability of AMS.

Amisulpride-CD-Loaded Liposomes: Optimization and In Vivo Evaluation.

Amisulpride (AMS) is an atypical antipsychotic agent used for the treatment of schizophrenia. The effect of different variables, i.e., the type of cyclodextrins (CDs), ratio of drug/CDs, and type of loading on the prepared AMS-CD liposomes (single and double loaded) was studied by applying 23 full factorial design. Double-loaded liposomes are loaded with AMS-hydroxyl propyl-β-cyclodextrin (HP-β-CD) in the aqueous phase and free drug in the lipophilic bilayer, while single-loaded liposomes are loaded only with AMS-HP-β-CD in the aqueous phase. Entrapment efficiency, particle size, polydespersibility, and zeta potential were selected as dependent variables. Design Expert® software was used to obtain an optimized formulation with high entrapment efficiency (64.55 ± 1.27%), average particle size of 40.1 ± 2.77nm, polydespersibility of 0.44 ± 0.37, and zeta potential of - 48.8 ± 0.28. Optimized formula was evaluated for in vitro release, surface morphology and stability study was also conducted. AMS-HP-β-CD in double-loaded liposomes exhibited higher drug release than those in the conventional liposomes and in the single-loaded liposomes. The maximum plasma concentration (Cmax) of AMS in optimized AMS-HP-β-CD double-loaded liposomal formulation increased by 1.55- and 1.29-fold, as compared to the commercial tablets and conventional liposomes, respectively. However, the relative bioavailability of AMS double-loaded liposomes was 1.94- and 1.28-folds of commercial tablet and conventional liposomes, respectively.

C-Fos expression in the hypothalamic paraventricular nucleus after a single treatment with a typical haloperidol and nine atypical antipsychotics: a pilot study.

The aim of the present study was to find out whether acute effect of different doses of selected antipsychotics including aripiprazole (ARI), amisulpride (AMI), asenapine (ASE), haloperidol (HAL), clozapine (CLO), risperidone (RIS), quetiapine (QUE), olanzapine (OLA), ziprasidone (ZIP), and paliperidone (PAL) may have a stimulatory impact on the c-Fos expression in the hypothalamic paraventricular nucleus (PVN) neurons. Adult male Wistar rats weighing 280-300 g were used. They were injected intraperitoneally with vehicle or antipsychotics in the following doses (mg/kg of b.w.): ARI (1, 10, 30), AMI (10, 30), ASE (0.3), HAL (1.0, 2.0), CLO (10, 20), RIS (0.5, 2.0), QUE (10, 20), OLA (5, 10), ZIP (10, 30), and PAL (1.0). Ninety min later, the animals were anesthetized with Zoletil and Xylariem and sacrificed by a transcardial perfusion with 60 ml of saline containing 450 μl of heparin (5000 IU/l) followed by 250 ml of fixative containing 4% paraformaldehyde in 0.1 M phosphate buffer (PB, pH 7.4). The brains were postfixed in a fresh fixative overnight, washed two times in 0.1 M PB, infiltrated with 30% sucrose for 2 days at 4 °C, frozen at -80 °C for 120 min, and cut into 30 μm thick serial coronal sections at -16 °C. c-Fos profiles were visualized by nickel intensified DAB immunohistochemistry and examined under Axio-Imager A1 (Zeiss) light microscope. From ten sorts of antipsychotics tested, only six (ARI-10, CLO-10 and CLO-20, HAL-2, AMI-30, OLA-10, RIS-2 mg/kg b.w.) induced distinct c-Fos expression in the PVN. The antipsychotics predominantly targeted the medial parvocellular subdivision of the PVN. The present pilot study revealed c-Fos expression increase predominantly in the PVN medial parvocellular subdivision neurons by action of only several sorts of antipsychotics tested indicating that this structure of the brain does not represent a common extra-striatal target area for all antipsychotics.

Comparison of social function, adverse reaction and medication adherence of Paliperidone, Amisulpride and Olanzapine in patients with first-episode schizophrenia

Objective To investigate the social function, adverse reaction and medication adherence of paliperidone, amisulpride, and olanzapine in patients with first episode schizophrenia. Methods A total of 96 patients with first episode of schizophrenia was randomly divided into three groups, with reference to random numbers, among which there were 32 in paliperidone group, 32 cases in amisulpride group, and 32 in olanzapine group. All the patients in all groups were assessed with negative and positive scale (PANSS), personal and social performance scale (PSP), drug attitude inventory (DAI) at baseline and the end of 6 months. Results ⑴ There was no significant difference in the therapeutic effect between three groups (P>0.05); ⑵ The scores of PSP and DAI were increased in three groups after treatment, and the difference was statistically significant compared to that before treatment (P<0.05). Conclusions Three drugs have similar efficacy in the treatment of first-episode schizophrenia, and there is no significant difference in improving medication compliance and social function. Key words: Antipsychotic agents/TU; Isoxazoles/AA; Isoxazoles/TU; Benzodiazepines/TU; Schizophrenia/DT; Treatment outcome

Response of Catatonia to Amisulpride and Lorazepam in an Adolescent with Schizophenia

Response of Catatonia to Amisulpride and Lorazepam in an Adolescent with Schizophenia

Ultra-high performance liquid chromatography tandem mass spectrometry method for detection of anti-schizophrenic drugs and the evaluation of their therapeutic reference ranges

Objective A highly feasible and reliable ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)method was presented for therapeutic drug monitoring of five anti-schizophrenic drugs (aripiprazole, amisulpride, olanzapine, paliperidone and ziprasidone) simultaneously and the reference range of plasma concentration was investigated. Methods establishment and evaluation. The selectivity, accuracy, precision, stability and linear range of established UPLC-MS/MS method were evaluated according to FDA and CLSI. After a ten-month clinical application, a retrospective analysis of 253 positive samples was carried out to investigate conformance of the AGNP therapeutic reference range for Chinese patients. Results The five anti-schizophrenic drugs could be simultaneously measured by the established UPLC-MS/MS within 6 minutes. The LOQs were 0.1 to 9.0 ng/ml. The correlation coefficients were all higher than 0.997 7. The intra-day and inter-day precisions were less than 11.1%, and the recoveries ranged from 86.2% to 104.8%. The clinical results suggested the good consistency in reference range with AGNP for olanzapine, aripiprazole, paliperidone and ziprasidone. While for amisulpride, the plasma concentration level (445.2±231.5) ng/ml was significantly higher than the AGNP-recommended range (100-320) ng/ml. Conclusion The established UPLC-MS/MS method was very suitable for monitoring anti-schizophrenic drugs.(Chin J Lab Med, 2017, 40: 787-792) Key words: Antipsychotic agents; Plasmaconcentration; Drug monitoring; Chromatography, high pressure liquid; Tandem mass spectrometry; Reference values

Comparison of curative effects of amisulpride and risperidone in the treatment of patients with first-episode schizophrenia

Objective To explore the effect of amisulpride and risperidone in the treatment of patients with first-episode schizophrenia and its influence on social function. Methods 70 patients of schizophrenia conformed to the International classification of diseases tenth edition(ICD-10) were randomly divided into amisulpride group(observation group, 35 cases) and risperidone group(control group, 35 cases) by using the random number table method. The Positive and Negative Scale(PANSS) was used to evaluate the efficacy, the Scale of Social Function in Psychosis Inpatients(SSPI) was used to evaluate social function before and after 8 weeks of treatment. Results After 8 weeks treatment, the negative symptom factor score of the PANSS in the observation group was (15.04±3.55)points, which was improved significantly compared with (17.82±3.87)points in the control group, the difference was statistically significant(t=3.132, P<0.05). The scores of the field in movement and interaction, social activities and skills factor score and the total score of SSPI in the observation group were (15.49±3.54)points, (14.53±4.25)points, (39.25±8.27)points, respectively, which in the control group were (12.78±3.29)points, (10.01±3.78)points, (33.72±7.83)points, respectively, the differences between the two groups were statistically significant (t=3.317, 4.701, 2.873, all P<0.05). Conclusion Amisulpride is effective in improving the negative symptoms, social function in patients with schizophrenia, and the effect is better than risperidone. Key words: Schizophrenia; Amisulpride; Risperidone

Development of novel amisulpride-loaded solid self-nanoemulsifying tablets: preparation and pharmacokinetic evaluation in rabbits

Objective: The current investigation is focused on the formulation and in vivo evaluation of optimized solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of amisulpride (AMS) for improving its oral dissolution and bioavailability.Methods: Liquid SNEDDS (L-SNEDDS) composed of Capryol™ 90 (oil), Cremophor® RH40 (surfactant), and Transcutol® HP (co-surfactant) were transformed to solid systems via physical adsorption onto magnesium aluminometasilicate (Neusilin US2). Micromeretic studies and solid-state characterization of formulated S-SNEDDS were carried out, followed by tableting, tablet evaluation, and pharmacokinetic studies in rabbits.Results: Micromeretic properties and solid-state characterization proved satisfactory flow properties with AMS present in a completely amorphous state. Formulated self-nanoemulsifying tablets revealed significant improvement in AMS dissolution compared with either directly compressed or commercial AMS tablets. In vivo pharmacokinetic study in rabbits emphasized significant improvements in tmax, AUC(0–12), and AUC(0–∞) at p < .05 with 1.26-folds improvement in relative bioavailability from the optimized self-nanoemulsifying tablets compared with the commercial product.Conclusions: S-SNEDDS can be a very useful approach for providing patient acceptable dosage forms with improved oral dissolution and biovailability.

Development of novel amisulpride-loaded liquid self-nanoemulsifying drug delivery systems via dual tackling of its solubility and intestinal permeability

Objective: The aim of the current investigation was at enhancing the oral biopharmaceutical behavior; solubility and intestinal permeability of amisulpride (AMS) via development of liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) containing bioenhancing excipients.Methods: The components of L-SNEDDS were identified via solubility studies and emulsification efficiency tests, and ternary phase diagrams were constructed to identify the efficient self-emulsification regions. The formulated systems were assessed for their thermodynamic stability, globule size, self-emulsification time, optical clarity and in vitro drug release. Ex vivo evaluation using non-everted gut sac technique was adopted for uncovering the permeability enhancing effect of the formulated systems.Results: The optimum formulations were composed of different ratios of Capryol™ 90 as an oil phase, Cremophor® RH40 as a surfactant, and Transcutol® HP as a co-surfactant. All tested formulations were thermodynamically stable with globule sizes ranging from 13.74 to 29.19 nm and emulsification time not exceeding 1 min, indicating the formation of homogenous stable nanoemulsions. In vitro drug release showed significant enhancement from L-SNEDDS formulations compared to aqueous drug suspension. Optimized L-SNEDDS showed significantly higher intestinal permeation compared to plain drug solution with nearly 1.6–2.9 folds increase in the apparent permeability coefficient as demonstrated by the ex vivo studies.Conclusions: The present study proved that AMS could be successfully incorporated into L-SNEDDS for improved dissolution and intestinal permeation leading to enhanced oral delivery.

Comparison of the efficacy of amisulpride and risperidone in the treatment of patients with first-episode schizophrenia

Objective To compare and analyze the efficacy and safety of amisulpride and risperidone in the treatment of patients with first-episode schizophrenia(FES). Methods 80 patients with FES were randomly divided into the observation group (n=40, orally given amisulpride) and the control group (n=40, orally given risperidone) according to random number table.The total effective rate, positive and negative symptoms scale (PANSS), adverse reaction rate of two groups were compared. Results 1 week after treatment, the negative symptoms score of the observation group was significantly lower than that of the control group[(20.89±3.07)points vs.(18.15±3.64)points, t=3.639, P=0.001].8 weeks after treatment, the PANSS scores and factor score of the two groups had no significant differences(all P>0.05). The total effective rate and adverse reaction rate of the observation group were 90.00%, 17.50% respectively, which of the control group were 82.50%, 27.50% respectively, there were no statistically significant differences (χ2=0.949, P=0.330; χ2=1.147, P=0.284). Conclusion Amisulpride and risperidone has similar efficacy and safety in the treatment of patients with FES, but amisulpride has better early effect in improving negative symptoms. Key words: Schizophrenia; Amisulpride; Risperidone

Female schizophrenia patients and risk of breast cancer: A population-based cohort study

ObjectiveBreast cancer is the most common type of cancer in women. This population-based cohort study aimed to examine the association between breast cancer in female schizophrenia patients and its association with the use of antipsychotics drugs. MethodsAll study subjects were selected from the Taiwan Insurance Claims Data (1998–2008). We compared the risk for breast cancer between female schizophrenia patients receiving antipsychotics (n=29,641) with female patients without any serious mental illnesses nor receiving antipsychotic drugs (n=59,282). We also compared between patients on 1) first-generation antipsychotics (FGAs) alone; 2) combination of first and second generation antipsychotics (SGAs); and 3) SGAs alone. We then stratified those on SGAs into two subgroups according to their prolactin-elevating properties: risperidone (RIS), paliperidone (PAL) or amisulpride (AMI) and all other SGAs. ResultsAfter adjusting for confounding factors, the risk of breast cancer in female schizophrenia patients was 1.94 higher than the non-schizophrenia cohort (aHR: 1.94, 95% CI: 1.43–2.63). Schizophrenia patients receiving a combination of FGAs and SGAs had a slightly higher risk of breast cancer than non-schizophrenic patients (aHR: 2.17, 95% CI: 1.56–3.01). Patients on RIS, PAL, and AMI had a 1.96-fold risk of breast cancer compared to the non-schizophrenic cohort (95% CI: 1.36–2.82). ConclusionsThis study raises awareness among both clinicians and patients about the importance of breast cancer screening and the promotion of healthy lifestyle choices. Due to the nature of our database, confounding factors – such as parity, obesity, hormone therapy, and smoking - could not be controlled for.

Antipsychotic Drugs Differentially Affect mRNA Expression of Genes Encoding the Neuregulin 1-Downstream ErbB4-PI3K Pathway

Background/Aims: The PIK3CD gene encodes the delta catalytic subunit of phosphoinositide 3-kinase (PI3K), an element of the neuregulin 1-downstream ErbB4-PI3K signaling pathway, which was recently identified as a molecular target for the treatment of schizophrenia. The aim of the study was to examine the effect of haloperidol (HALO), clozapine (CLO), olanzapine (OLA), quetiapine (QUE) and amisulpride (AMI) on the mRNA and protein expression of genes encoding the elements of ErbB4-PI3K pathway, in a human central nervous system cell line. Methods: The U-87MG human glioblastoma cell line was used as an experimental model. Quantitative polymerase chain reaction was used to examine the expression of mRNA and enzyme-linked immunosorbent assay for protein expression. Results: At concentrations reached in clinical settings in the brain, CLO, as well as OLA and QUE to a lesser extent, but not AMI and probably not HALO, decreased the mRNA expression of PIK3CD. Protein expression of the gene did not confirm the mRNA expression profile. Conclusions: The tested antipsychotic drugs (APDs) in the U-87MG glioblastoma cell line differentially regulates the mRNA expression of PIK3CD; however, the protein expression does not confirm these findings. The results of the study may help deepen the understanding of the mechanism of action of APDs.