Formulation Optimization of Citalopram Hydrobromide Thermosensitive Nasal Gel and Its In Vitro Properties / 中国药学杂志

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.

Pharmacokinetics and Brain Delivery of Citalopram Hydrobromide Thermosensitive Nasal Gel in Rats / 中国药学杂志

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.

New Ringer's lactate gel formulation on nasal comfort and humidification / Nova formulação de Ringer lactato gel no conforto e umidificação nasal

Abstract Introduction: The use of saline irrigation for nasal washes is a well established procedure in the treatment of sinonasal inflammation and infection. In addition to saline solutions, Ringer's lactate is also an efficient option for nasal washes and humidification. Objective: To assess the comfort, humidification and tolerance regarding stinging sensation, provided by sodium chloride nasal gel at the concentrations of 4.5 mg/g and 6.0 mg/g through questionnaires answered by the patients. Methods: A total of 60 patients, 56 females, aged between 22 and 66 years old (mean age of 47) and 4 males, aged between 36 and 66 years (mean age of 49), were included in the study for a period of 17 days (±2 days) treatment. The patients were monitored by a general practitioner throughout the study period. They were instructed to apply each product in both nostrils twice a day during a 7-day period (±2 days). The patients were evaluated prior to the use of the first product at visit 0 (V0), after 7 days of treatment (±2 days) at visit 1 (V1), after 3 days of product discontinuation at visit 2 (V2) and after 7 days (±2 days) of treatment with the second product, in visit 3 (V3). Results: A significant difference (5% significance) was observed regarding comfort and stinging sensation between the two different concentrations; comfort was higher and stinging was lower with the 6.0 mg/g concentration gel. No difference in humidification was observed between the two treatments. Conclusion: Ringer's lactate at the concentration of 6.0 mg/g was superior to that at 4.5 mg/g for parameters comfort and stinging sensation. No statistical difference was observed between the two products regarding nasal humidification.

Resumo Introdução: O uso de soluções salinas para lavagem nasal está consagrado no tratamento de quadros inflamatórios e infecciosos nasossinusais. Além das soluções salinas, o ringer lactato é uma importante opção tanto para lavagem quanto para a hidratação nasal. Objetivo: Avaliar a tolerabilidade (ardência e conforto) e umidificação do produto gel nasal cloreto de sódio 4,5 mg/g em relação ao ringer lactato 6,0 mg/g, por meio de questionários respondidos pelos pacientes. Método: Foram incluídos 60 pacientes, 56 mulheres (22-66 anos; média: 47 anos) e quatro homens (36-66 anos; média: 49 anos) foram incluídos no estudo de 17 dias (± 2 dias) de tratamento. Os pacientes foram supervisionados por um clínico geral durante todo o período do estudo. Os pacientes usaram os produtos com uma borrifada em cada narina duas vezes ao dia, durante sete dias (± 2 dias). As formulações foram avaliadas antes do uso do primeiro produto na visita 0 (V0), após sete dias (± 2 dias) de tratamento na visita 1 (V1), após três dias de interrupção do primeiro tratamento na visita 2 (V2) e após sete dias (± 2 dias) de uso do segundo produto na visita 3 (V3). Resultados: Foi observada diferença significante para o conforto das vias nasais, (significância de 5%), na comparação entre os tratamentos nos atributos de conforto e ardência. O conforto das vias nasais foi superior e a ardência inferior para o gel nasal ringer lactato 6,0 mg/g em comparação ao gel cloreto de sódio 4,5 mg/g. Não foi observada diferença significante para a umidificação entre os tratamentos. Conclusão: O gel ringer lactato 6,0 mg/g foi superior ao produto gel cloreto de sódio 4,5 mg/g nos quesitos conforto e ardência. Não foi observada diferença estatisticamente significante entre os tratamentos em relação à umidificação das vias nasais.

Pharmacokinetics and Brain Targeting Characteristics of Risperidone Nasal Gel in Rats / 中国药学杂志

OBJECTIVE: To study the pharmacokinetics of risperidone (RIS) nasal gel and its brain targeting effect and related mechanisms in rats. METHODS: The concentrations of RIS in rat plasma and brain tissues were determined by HPLC method. The pharmacokinetics and relative bioavailability to oral RIS preparation of RIS nasal gel and the drug distribution in various brain tissues such as olfactory bulb (OB), olfactory tract (OT), cerebellum (CL) and cerebrum (CR) were investigated in rats. RESULTS: The main pharmacokinetic parameters of RIS following nasal and oral administration such as tmax and ρmax were 5 and 20 min, 9.89 and 1.93 μg·mL-1, respectively. The relative bioavailability of nasally administered RIS was up to 4 730%. Furthermore, the AUC values of RIS nasal gel for different brain tissues such as OB, OT, CL and CR were found to be 45.3, 9.9, 1.5 and 1.1 folds of those of oral drug suspension, respectively. CONCLUSION: The in vivo absorption rate and bioavailability of RIS following nasal administration are obviously increased and improved. Additionally, the significant brain targeting characteristics of the drug nasal gel is also confirmed.

Preparation and in vitro quality evaluation of risperidone nasal gel / 中国药学杂志

OBJECTIVE: To prepare a nasal gel of risperidone (RIS) and evaluate its in vitro quality. METHODS: The formulation and preparation process of RIS nasal gel were optimized with orthogonal test using appearance,spreading ability and in vitro release as main evaluation indexes. The quality items of the optimized RIS nasal gel such as appearance,pH value,contents of RIS and preservative,in vitro release and related substances were then evaluated. RESULTS: The optimal formulation of the RIS nasal gel consisted of 0.5% RIS, 0.35% carbopol 940, 0.5% chlorobutanol,20% propanediol and 15% DM-β-CD and appropriate amount of purified water. Its ideal pH value was about 6.0. Furthermore,the quality items such as the appearance,pH value,contents of RIS and preservative,in vitrorelease and related substances of the preparation all conformed to the relevant quality requirements in China Pharmacopiea (2010). CONCLUSION: The RIS nasal gel will be a promising new preparation for nasal administration due to its reasonable formulation,simple preparation process and controllable quality.

Preparation and Quality Control of Thermosensitive Nasal Gel of Ephedrine Hydrochloride and Diphen-hydramine Hydrochloride / 中国药师

Objective:To prepare the thermosensitive nasal gel of ephedrine hydrochloride and diphenhydramine hydrochloride and establish its quality control method. Methods:The amounts of P407, P188 and PEG 6000 were optimized by an orthogonal test with the gelling temperature as the index. An HPLC method was established to determine the contents of ephedrine hydrochloride and di-phenhydramine hydrochloride. Results:The optimum amount of P407, P188 and PEG 6 000 was 19%, 2% and 1%, respectively. The linear range of ephedrine hydrochloride was 1.600 0-2.400 0 mg·ml-1(r=0.999 6), and the average recovery was 99.76%with RSD of 1. 02%(n=9). The linear range of diphenhydramine hydrochloride was 0. 160 0-0. 240 0 mg·ml-1(r=0. 999 7), and the average recovery was 101. 27% with RSD of 1. 10%(n=9). Conclusion:The formula design and preparation technology of the gel are feasible. The HPLC method is suitable for the quality control of the preparation.

Factors Influencing the Release in Vitro of Atenolol Nasal Gel / 中国药房

OBJECTIVE:To investigate the factors influencing the drug release of atenolol nasal gel for references of optimization of its formulation.METHODS:The effects of carbopol 941(0.8%,1.0% and 1.2%)which used as the gel stroma,the amount of surface acting agent Tween-80(0,6% and 8%),and absorption enhancer(DM-?-CD vs.?-CD)on the in vitro release of atenolol nasal gel were investigated.RESULTS:All the above-mentioned 3 factors had marked effects on the in vitro release of atenolol nasal gel.The in vitro release of atenolol nasal gel was markedly enhanced by 0.8% carbopol 941,6% Tween-80 and 10% DM-?-CD absorption enhancer.CONCLUSION:The results in the study serve as references for the optimization of the formulation of atenolol nasal gel.

Preparation of Quality Control of Chloramphenicol and Ephedrine Nasal Gel / 中国药房

OBJECTIVE:To prepare chloramphenicol and ephedrine nasal gel and establish its quality control method.METHODS:Gel was prepared with chloramphenicol and ephedrine hydrochloride as principal agents and with carbomer-940 as base.The contents of the principal agents were determined by HPLC and the stability of the gel was investigated as well.RESULTS:The preparation was transparent colloid.The linear ranges of chloramphenicol and ephedrine hydrochloride were 62.5～1 000 and 31.25～500 ?g?L-1(r=0.999 9),respectively,with average recovery rates at 99.64%(RSD=0.5%)and 99.57%(RSD=0.7%),respectively.Storing under room temperature,no obvious change was noted for the property of the sample at 12 months.CONCLUSION:The preparation technique of the gel is simple and feasible,and its quality is stable and controllable.