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OBJECTIVE: To optimize the formulation of citalopram hydrobromide (CTH ) thermosensitive nasal gel and further evaluate its in vitro properties. METHODS: With gelling temperature and gelling time as evaluating indexes, central composite design-response surface and single factor experimental design method were used to optimize the formulation of CTH thermosensitive nasal gel by using poloxamer 407(F127) and carbomer 940 (CP940) as gel materials. Meanwhile, nasal mucosa permeation enhancer for CTH was then sieved by using Franz diffusion cell and ex vivo sheep nasal mucosa as experimental model. Finally, CTH thermosensitive nasal gel was prepared with cold method and then its in vitro properties was evaluated. In vitro cumulative erosion and cumulative release rate of the drug thermosensitive nasal gel were investigated by membrane-free dissolution method and dialysis membrane method, respectively. Moreover, the effect of temperature and pH on the viscosity of the drug nasal gel formulation was also evaluated. RESULTS: The optimal formulation of the thermosensitive nasal gel consisted of CTH 8.0%, F127 20.27%, CP940 0.17%, DM-β-CD 3.0%, ethylparaben 0.05% and distilled water. The gelling temperature, gelling time and pH of the drug thermosensitive nasal gel were found to be about 32.5 ℃,42 s and 5.0, respectively. The in vitro cumulative erosion and cumulative release percentage were both greater than 90% in 55 min and furthermore there was good linear correlation between these two parameters (r=0.998 6). Additionally, in vitro cumulative release of the drug from the gel formulation was determined to be 92% within 8 h, which conformed to Higuchi kinetic equation. Furthermore, the viscosity of the drug nasal gel was influenced by temperature as well as pH in different extent. CONCLUSION: The optimized formulation of the CTH thermosensitive nasal gel with central composite design-response surface method and single factor design method shows suitable gelling temperature, gelling time, pH value for nasal preparation and obvious in vitro drug sustained release characteristics.
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OBJECTIVE: To investigate the pharmacokinetics of citalopram hydrobromide(CTH)thermosensitive nasal gel and further evaluate its brain delivery in rats. METHODS: The concentrations of CTH in rat plasma and brain tissue were determined by HPLC method. With intragastric administration (ig) of CTH solution as control, CTH thermosensitive nasal gel was intranasally given to rats and the concentrations of CTH in plasma and brain tissues were then determined. Moreover, the main pharmacokinetic parameters of CTH in plasma and brain tissues such as tmax, ρmax,relative bioavailability (Fr) and drug targeting efficiency (DTE) were estimated. RESULTS: Main pharmacokinetic parameters of CTH following nasal and ig administration to rats such as tmax and ρmax were 5 and 45 min, 2 152.86 and 589.68 ng•mL-1 in plasma, and 5 and 45 min, 17 660.56 and 1 171.68 ng•g-1 in brain tissue, respectively. Finally, the Fr and DTE of CTH thermosensitive nasal gel were found to be 184.91% and 250.03%, respectively. CONCLUSION: CTH thermosensitive nasal gel may be an ideal non-oral new dosage form with many advantages such as rapid in vivo absorption, high bioavailability and obvious brain delivery characteristics.
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Objective To investigate the effect of citalopram hydrobromide tablets on cognitive function and inflammatory factors in patients with recurrent bipolar disorder (BPD),and to analyze its possible mechanism of action.Methods 104 patients with recurrent BPD in our hospital from July 2014 to December 2015 were selected,and they were divided into observation group and control group by random number table,52 cases in each group.Control group was given sodium valproate,while observation group was given citalopram hydrobromide tablets and sodium valproate.After 8-week treatment,the emotional state,cognitive function,inflammatory factors were compared between the two groups.Results Before treatment,HAMD score,BPMS score of two groups were not statistically significant.After 8 weeks of treatment,HAMD score and BPMS score of two groups were significantly lower than those in the same group before treatment (P ＜ 0.01);and the observation group HAMD score and BPMS score were significantly lower than the control group (P ＜ 0.01).Before treatment,TMT-A,TMT-B time of two groups were not statistically significant.After 8 weeks of treatment,TMT-A and TMT-B time of two groups were significantly shorter than the same group before treatment (P ＜ 0.05).TMT-A TMT-B in the observation group were significantly shorter than the control group (P ＜ 0.05).The content of serum MIF,IL-1 beta and IL-6 in two groups before treatment were not statistically significant.After 8 weeks of treatment,the contents ofMIF,IL-1 beta,IL-6 in two groups were significantly lower than the same group before treatment (P ＜ 0.05).And the levels of serum MIF,IL-1 beta,IL-6 in observation group were significantly lower than the control group (P ＜ 0.05).Conclusion Citalopram hydrobromide tablets can relieve clinical symptoms,improve cognitive function,and it possibly has relations with inhibiting the expression of inflammatory factors.
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Objective: To observe the efficacy of Modified Chaihu Shugan Granule on post ischemic stroke depression (PSD) patients, and to explore its effect on serum brain-derived neurotrophic factor (BDNF). Methods: Totally 100 patients with PSD were randomly devided into treatment group (50 cases) and control group (50 cases). Both groups were given the conventional treatment of ischemic cerebrovascular disease, while the control group also took citalopram hydrobromide, once a day, 20 mg each time. Additionally, the treatment group was given Modified Chaihu Shugan Granule. The therapeutic course for all was 8 weeks. Before treatment and 4, 8 weeks after treatment, scores of Hamilton depression rating scale (HAMD) and Barthel Index of both groups were observed to evaluate clinical effects. Serum levels of BDNF were detected at the same time. Results: Total effective rate of clinical effects in the treatment group (94.00%) was better than that of the control group (72.00%) (P<0.05). Compared with before treatment in the same group, HAMD scores all obviously decreased but the scores of Barthel Index and serum levels of BDNF increased (P<0.01), while those after the treatment for 8 weeks showed greater improvements (P<0.01). Separately, HAMD scores of the treatment group were lower than those of the control group at 4 and 8 weeks after the treatment (P<0.01), while the scores of Barthel Index increased all along (P<0.01). Serum levels of BDNF in the treatment group were obviously higher than those in the control group at 4 weeks after the treatment (P<0.05), while it was a significant difference at 8 weeks (P<0.01). Conclusion: Modified Chaihu Shugan Granule used for treating the patients with PSD could improve the clinical efficacy, activities of daily living, and depressive state. Its mechanism might be associated with inhibiting serum levels of BDNF.
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OBJECTIVE:To compare the pharmacokinetics and bioavailability between domestic(test)and imported(reference)citalopram hydrobromide tablets and to evaluate the bioequivalence of the two preparations.METHODS:A single dose of 40 mg test tablet or reference tablet of citalopram hydrobromide was administered by randomized crossover way in 20 healthy male volunteers and the plasma concentrations of the citalopram hydrobromide were determined by HPLC.The pharmacokinetic parameters were calculated with 3p97 pharmacokinetic program and the bioavailability was evaluated.RESULTS:The concentration-time curves of two preparations fitted two compartment mode1.The pharmacokinetic parameters of the test preparation versus the reference preparation were as follows,Cmax:(147.00?86.04)ng?mL-1 vs.(154.13?87.57)ng?mL-1;tmax:(4.55?1.35)h vs(4.75?1.65)h;AUC0～196:(6 590.69 ? 1 866.00)ng?h?mL-1 vs.(7 156.26?2 181.18)ng?h?mL-1;AUC0～∞:(7 767.56?2 193.92)ng?h?mL-1 vs.(8 433.45?2 631.88)ng?h?mL-1.The relative bioavailability of the test citalopram hydrobromide tablet was(92.10?18.68)%.CONCLUSION:The domestic and the reference citalopram hydrobromide tablet are bioequivalent.