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Duan X.,District Delivery | Ning M.,District Delivery
Indian Journal of Pharmaceutical Sciences | Year: 2015

Preparation and in vitro/in vivo evaluation of mifepristone intravaginal ring formulations were investigated. In the present study, it is reported that a mifepristone intravaginal ring of reservoir design comprising of a mifepristone silicone elastomer core enclosed in a silicone layer. During the preparation of intravaginal ring solid dispersion method was employed which improved the release rate of drug from the intravaginal ring. In vitro release studies performed under sink conditions and the released drug amounts were estimated using UV spectrometry at 310 nm. In addition, the in vivo release profile of in-house devices was evaluated in female New Zealand white rabbits. The rabbit plasma samples were processed and analyzed using a validated HPLC-MS method. Norgestrel was used as internal standard, and plasma samples contained mifepristone and internal standard were deproteinized, and then subjected to HPLC-MS analysis under condition of electrospray ionization in the selected ion monitoring mode. The drug release from intravaginal ring made in house was constant for 21 days in rabbits, which suggested the mifepristone intravaginal ring release system would be useful in clinical practice in the future. The result indicated the in vitro/in vivo correlation is perfect, which explained in vitro release analysis method developed was feasible.


Li C.,District Delivery | Ning M.,District Delivery | Yao X.,District Delivery | Wang Y.,Shenyang Pharmaceutical University | Liu Y.,District Delivery
Pakistan Journal of Pharmaceutical Sciences | Year: 2016

Preparation and in vitro/in vivo evaluation of gestodene (GEST) intravaginal ring (IVR) formulations which can release a constant dose of GEST during 3 weeks were investigated. In present study a reservoir gestodene intravaginal ring, including a gestodene silicone elastomer core and the non-active silicone layer, was reported, which was manufactured by reaction injection moulding at 80oC for 20 min. The raw materials compatibility experiments showed that the silicone elastomer core carrier wouldn't interact with drugs. In vitro release samples were determined by HPLC and the experiment was performed under sink conditions. The equation of cumulative release verse time was Y=64.76x+5.44 (r=0.9998), performing zero-order release at about the target dose of 60 μg/day over 21 days. Drug release increased with temperature elevating from 45 to 55oC, which could be attributed to optimizing the prescription. In addition, the pharmacokinetic and safety studies of gestodene intravaginal ring were evaluated in female New Zealand White rabbits. The GEST in plasma was analyzed by LC-MS/MS and the results proved that the correlation between in vitro and in vivo was relatively well.


Xu L.-X.,Yantai University | Xu L.-X.,District Delivery | Wang T.-T.,District Delivery | Geng Y.-Y.,Yantai University | And 8 more authors.
Analytical and Bioanalytical Chemistry | Year: 2017

The direct analysis of drug distribution of rotigotine-loaded microspheres (RoMS) from tissue sections by liquid extraction surface analysis (LESA) coupled with tandem mass spectrometry (MS/MS) was demonstrated. The RoMS distribution in rat tissues assessed by the ambient LESA-MS/MS approach without extensive or tedious sample pretreatment was compared with that obtained by a conventional liquid chromatography tandem mass spectrometry (LC-MS/MS) method in which organ excision and subsequent solvent extraction were commonly employed before analysis. Results obtained from the two were well correlated for a majority of the organs, such as muscle, liver, stomach, and hippocampus. The distribution of RoMS in the brain, however, was found to be mainly focused in the hippocampus and striatum regions as shown by the LESA-imaged profiles. The LESA approach we developed is sensitive enough, with an estimated LLOQ at 0.05 ng/mL of rotigotine in brain tissue, and information-rich with minimal sample preparation, suitable, and promising in assisting the development of new drug delivery systems for controlled drug release and protection. [Figure not available: see fulltext.] © 2017 Springer-Verlag Berlin Heidelberg


Liang D.-S.,Peking University | Liang D.-S.,District Delivery | Su H.-T.,Peking University | Su H.-T.,District Delivery | And 7 more authors.
Biomaterials | Year: 2015

Poor site-specific delivery and incapable deep-penetration into tumor are the intrinsic limitations to successful chemotherapy. Here, the tumor-homing penetrating peptide tLyP-1-functionalized nanoparticles (tLPTS/HATS NPs), composed of two modularized amphiphilic conjugates of tLyP-1-PEG-TOS (tLPTS) and TOS-grafted hyaluronic acid (HATS), had been fabricated for tumor-targeted delivery of docetaxel (DTX). The prepared tLPTS/HATS NPs had about 110 nm in mean diameter, high drug encapsulation efficiency (93%), and sustained drug release behavior. In vitro studies demonstrated that the tLPTS/HATS NPs exhibited enhanced intracellular delivery and much better anti-invasion ability, cytotoxicity, and apoptosis against both invasive PC-3 and MDA-MB-231 cells as compared to the non-tLyP-1-functionalized HATS NPs. The remarkable penetrability and inhibitory effect on both PC-3 and MDA-MB-231 multicellular tumor spheroids were also identified for the tLPTS/HATS NPs. In vivo biodistribution imaging demonstrated the tLPTS/HATS NPs possessed much more lasting accumulation and extensive distribution throughout tumor regions than the HATS NPs. The higher in vivo therapeutic efficacy with lower systemic toxicity of the tLPTS/HATS NPs was also verified by the PC-3 xenograft model in athymic nude mice. These results suggested that the designed novel tLPTS/HATS NPs were endowed with tumor recognition, internalization, penetration, and anti-invasion, and thus might be a promising anticancer drug delivery vehicle for targeted cancer therapy. © 2015 Elsevier Ltd.


Goedert J.D.,University of Nebraska - Lincoln | Sekpe V.D.,District Delivery
Journal of Construction Engineering and Management | Year: 2013

This paper presents a conceptual approach to scheduling multiple projects in a matrix organization with rapidly changing and sometimes competing objectives using the analytical hierarchy process (AHP) within a decision support system (DSS). This approach increased the analytical capabilities and scheduling efficacy of traditional scheduling processes in a medium-sized electric utility company. The purpose of this paper is to establish a logical framework for scheduling multiple projects with competing priorities while taking into account all known corporate organizational constraints. Traditional scheduling techniques such as the program evaluation and review technique and critical-path method are heavily based on time constraints and resource availability, neglecting factors such as customer satisfaction, organizational financial objectives, political risks, and other intangible parameters that greatly influence scheduling processes. The primary contribution of this paper is a conceptual framework that offers a platform to incorporate tangible and intangible variables into a decision support system using AHP for scheduling multiple projects with competing objectives in matrix organizations. The results of the application showed that, when compared with traditional scheduling methods, this DSS model with integrated AHP showed improvements in prioritizing in accordance with political risks, cash-flow demands, and crew allocation. It appears to be a superior solution for solving prioritization issues in matrix organizations. © 2013 American Society of Civil Engineers.


Zhang Y.,District Delivery | Li C.-X.,District Delivery | Li C.-X.,Peking Union Medical College | Ning M.-Y.,District Delivery | And 2 more authors.
Advances in Pharmacological Sciences | Year: 2013

In the present study, we investigated the feasibility of the vaginal administration of drospirenone silicone IVR. The in vitro release characteristics of matrix-type and reservoir-type IVR were compared under sink conditions in 21 days. At the same time, API excipients compatibility and preformulation study was performed by HPLC, IR, and DSC methods. Biocompatibility of reservoir system was evaluated by tolerability on tissue level in rats. It was found that, under strong light exposure, high temperature, and high humidity conditions, drospirenone and excipients had no significant interactions. The daily release of reservoir-type IVR was about 0.5 mg/d sustaining 21 days, which significantly decreased the burst effect compared with the matrix system. When drospirenone was modified by the PVPk30 in the reservoir system formulation, the daily release rate increased to 1.0 mg/d sustaining 21 days. The cumulative release of reservoir-type IVR was fitted to zero release equation. In addition, biocompatibility of drospirenone IVR system in this dosage is safe. It is feasibility feasibile to further developed for safe, convenient, and effective contraceptive drug delivery with reduced dosing interval. © 2013 Ying Zhang et al.


Ning M.,District Delivery | Zhou Y.,District Delivery | Chen G.,District Delivery | Mei X.,Beijing Institute of Pharmacology and Toxicology
Advances in Pharmacological Sciences | Year: 2011

Preparation and in vitro and in vivo evaluation of vinpocetine (VIN) elementary osmotic pump (EOP) formulations were investigated. A method for the preparation of VIN elementary osmotic pump tablet was obtained by adding organic acid additives to increase VIN solubility. VIN was used as the active pharmaceutical ingredient, lactose and mannitol as osmotic agent. Citric acid was used as increasing API solubility and without resulting in the API degradation. It is found that the VIN release rate was increasing with the citric acid amount at a constant range. Cellulose acetate 398-3 was employed as semipermeable membrane containing polyethylene glycol 6000 and diethyl-o-phthalate as pore-forming agent and plasticizer for controlling membrane permeability. In addition, a clear difference between the pharmacokinetic patterns of VIN immediate release and VIN elementary osmotic pump formulations was revealed. The area under the plasma concentration-time curve after oral administration of elementary osmotic pump formulations was equivalent to VIN immediate release formulation. Furthermore, significant differences found for mean residence time, elimination half-life, and elimination rate constant values corroborated prolonged release of VIN from elementary osmotic pump formulations. These results suggest that the VIN osmotic pump controlled release tablets have marked controlled release characters and the VIN osmotic pump controlled release tablets and the normal tablets were bioequivalent. Copyright © 2011 Meiying Ning et al.


PubMed | District Delivery
Type: | Journal: Advances in pharmacological sciences | Year: 2011

Preparation and in vitro and in vivo evaluation of vinpocetine (VIN) elementary osmotic pump (EOP) formulations were investigated. A method for the preparation of VIN elementary osmotic pump tablet was obtained by adding organic acid additives to increase VIN solubility. VIN was used as the active pharmaceutical ingredient, lactose and mannitol as osmotic agent. Citric acid was used as increasing API solubility and without resulting in the API degradation. It is found that the VIN release rate was increasing with the citric acid amount at a constant range. Cellulose acetate 398-3 was employed as semipermeable membrane containing polyethylene glycol 6000 and diethyl-o-phthalate as pore-forming agent and plasticizer for controlling membrane permeability. In addition, a clear difference between the pharmacokinetic patterns of VIN immediate release and VIN elementary osmotic pump formulations was revealed. The area under the plasma concentration-time curve after oral administration of elementary osmotic pump formulations was equivalent to VIN immediate release formulation. Furthermore, significant differences found for mean residence time, elimination half-life, and elimination rate constant values corroborated prolonged release of VIN from elementary osmotic pump formulations. These results suggest that the VIN osmotic pump controlled release tablets have marked controlled release characters and the VIN osmotic pump controlled release tablets and the normal tablets were bioequivalent.


PubMed | District Delivery and Shenyang Pharmaceutical University
Type: Journal Article | Journal: Pakistan journal of pharmaceutical sciences | Year: 2016

Preparation and in vitro/in vivo evaluation of gestodene (GEST) intravaginal ring (IVR) formulations which can release a constant dose of GEST during 3 weeks were investigated. In present study a reservoir gestodene intravaginal ring, including a gestodene silicone elastomer core and the non-active silicone layer, was reported, which was manufactured by reaction injection moulding at 80C for 20 min. The raw materials compatibility experiments showed that the silicone elastomer core carrier wouldnt interact with drugs. In vitro release samples were determined by HPLC and the experiment was performed under sink conditions. The equation of cumulative release verse time was Y=64.76+5.44 (r=0.9998), performing zero-order release at about the target dose of 60 g/day over 21 days. Drug release increased with temperature elevating from 45 to 55C, which could be attributed to optimizing the prescription. In addition, the pharmacokinetic and safety studies of gestodene intravaginal ring were evaluated in female New Zealand White rabbits. The GEST in plasma was analyzed by LC-MS/MS and the results proved that the correlation between in vitro and in vivo was relatively well.

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