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.

Pharmacodynamic comparison of prostaglandin E1 administered by different routes to rats / 药学学报

The pharmacodynamics of prostaglandin E1 (PGE1) administered by different routes to rats was investigated in this paper. The hypotensive effect of PGE, was used as an index of drug efficacy, pharmacodynamic parameters such as time to reach peak effect (Tmax), maximal percentage of blood pressure decrease (Emax, %), duration of effect (Td), and the area under the blood pressure decrease percent-time curves (AUC, % x min) were determined after PGE1 given to rats intranasally, sublingually, intraperitoneally (ip), and intramuscularly (im), separately, and compared with those obtained from intravenous (iv) administration. Similar to iv route, the pharmacodynamic parameters of PGE1 from the other administration routes, Emax, Td and in particular AUC values were all increased with increasing doses, showing dose-efficacy relationship. Tmax was found to be approximately 3-4 min for nasal route, 3-8 min for im, 6-8 min for ip and 12-30 min for sublingual route, separately. Thus, the order of magnitude of absorption rate of the drug was as follows: nasal approximately = im > ip > sublingual. If the pharmacological bioavailability (PF) for each administration route was used as a tentative measure of drug absorption extent, the order of magnitude of absolute bioavailability appeared as follows: nasal > im approximately = ip > sublingual. Furthermore, the interindividual difference was found to be larger for im and ip route than that for nasal and sublingual route. These results indicate nasal and sublingual routes are two promising routes for the systemic delivery of PGE1 in clinical applications.

The complexation of prostaglandin E1 with hydroxylpropyl-beta-cyclodextrin in aqueous solution / 药学学报

<p><b>AIM</b>To investigate the complexation of prostaglandin E1 (PGE1) with hydroxylpropyl-beta-cyclodextrin (HP-beta-CD) in aqueous solutions, inclusion molar ratio of the host and guest molecules and change of thermodynamic parameters during the complexation process.</p><p><b>METHODS</b>The measurements of the complexation mechanism, inclusion molar ratio of the host and guest molecules and change of thermodynamic parameters were carried out by the following methods separately: phase solubility method, UV absorption spectroscopy, circular dichroism spectroscopy, equimolar series method and thermodynamic method, respectively.</p><p><b>RESULTS</b>That all the phase solubility diagrams showed a typical AL-type in various pH buffered solutions, suggested the formation of a soluble complex of 1:1 molar ratio. Both UV absorption spectroscopy and circular dichroism spectroscopy confirmed that the significant interaction between the host and guest molecules was probably due to the inclusion of chromophore moiety of PGE1 molecule into the hydrophobic cavity of HP-beta-CD molecule. The change in the thermodynamic parameters suggested that the complexation could proceed spontaneously along with the release of heat and the decrease of entropy.</p><p><b>CONCLUSION</b>An 1:1 molar ratio inclusion complex of PGE1 with HP-beta-CD could be formed spontaneously and, hence, the solubility of PGE1 in aqueous solution increased. Appropriate temperature and suitable media pH probably favor the progress of complexation procedure.</p>