Factors affecting nasal drug delivery and design strategies for intranasal drug delivery / 浙江大学学报·医学版

Intranasal drug delivery system is a non-invasive drug delivery route with the advantages of no first-pass effect, rapid effect and brain targeting. It is a feasible alternative to drug delivery via injection, and a potential drug delivery route for the central nervous system. However, the nasal physiological environment is complex, and the nasal delivery system requires "integration of medicine and device". Its delivery efficiency is affected by many factors such as the features and formulations of drug, delivery devices and nasal cavity physiology. Some strategies have been designed to improve the solubility, stability, membrane permeability and nasal retention time of drugs. These include the use of prodrugs, adding enzyme inhibitors and absorption enhancers to preparations, and new drug carriers, which can eventually improve the efficiency of intranasal drug delivery. This article reviews recent publications and describes the above mentioned aspects and design strategies for nasal intranasal drug delivery systems to provide insights for the development of intranasal drug delivery systems.

Investigation of Intestinal Absorption Characteristics of Multi-index Components of Danggui Buxuetang Based on Drug Absorption Simulating System / 中国实验方剂学杂志

ObjectiveTo investigate the intestinal absorption characteristics of multi-index components in Danggui Buxuetang with drug absorption simulating system （DASS） established by everted intestinal sac model. MethodThe intestinal absorption solution at different time points after administration of Danggui Buxuetang was collected and detected by high performance liquid chromatography （HPLC）， acetonitrile （A）-0.2% glacial acetic acid solution （B） was used as the mobile phase for gradient elution （0-16 min， 15%-23%A； 16-20 min， 23%-28%A； 20-25 min， 28%-30%A； 25-30 min， 30%A； 30-35 min， 30%-65%A； 35-45 min， 65%-95%A）， the detection wavelength was 302 nm. HPLC fingerprint of intestinal absorption solution was established and the common peak was calibrated， and the relative cumulative absorption rate of each index component was calculated. The relative cumulative absorption curves of components were fitted with various mathematical models by DDSolver 1.0 to explore the absorption law of different components. ResultThe absorption process of C2 （calycosin-7-glucoside） and C6 in Danggui Buxuetang was in line with zero-order equation， C9 was best fitted by Weibull equation， and the remaining 7 components were in line with Makoid-Banakar equation. C1 with C2， C3， C5， C7 and C10， C2 with C5 and C7， C3 with C4， C5， C7 and C10， C4 with C6 and C10， C5 with C7， C6 with C10， C7 with C10， C8 with C9 were absorbed simultaneously during the absorption process. With the prolongation of time， the overall cumulative absorption rate of Danggui Buxuetang increased. At 120 min， the overall cumulative absorption rate of Danggui Buxuetang exceeded 38%， and reached 49.14% at 180 min. ConclusionTen ingredients in Danggui Buxuetang are absorbed in the jejunum， but absorption law of various components is different， which shows that the intestinal absorption of compound preparations of traditional Chinese medicine （TCM） has multiple characteristics. Intestinal absorption study of TCM compound preparations with chemical composition as the index can reveal some of its absorption law， but it is not complete.

Study on borneol combined with astragaloside IV and Panax notoginseng saponins promoting bioactive components into brain in cerebral ischemia/reperfusion model of rats / 中草药

Objective To investigate whether borneol can promote the bioactive components of the combination of astragaloside IV (AST IV) and Panax notoginseng saponins (PNS) into the blood-brain barrier of rats with middle cerebral artery occlusion (MCAO)/reperfusion. Methods Using the model of MCAO/reperfusion, rats were randomly divided into sham-operation group, model group, borneol group, AST IV group, PNS group, AST IV + PNS group and borneol + AST IV + PNS group, and the content of AST IV and the bioactive components of PNS (ginsenoside Rg1, ginsenoside Rb1, and notoginsenoside R1) in the cerebral cortex and the cerebellum of the affected side and the healthy side were determined by liquid chromatography-mass spectrometry (LC-MS/MS). Results AST IV, whether used alone or combined with PNS and borneol, was mainly distributed in the cerebral cortex after oral administration, especially in the affected cerebral cortex. Borneol combined with AST IV and PNS significantly increased the content of AST IV in the affected and the healthy cerebral cortex. The bioactive components of PNS such as ginsenoside Rg1, ginsenoside Rb1, and notoginsenoside R1 was mainly distributed in the affected side of the cerebellum when PNS was used alone. Borneol combined with AST IV + PNS significantly increased the content of ginsenoside Rb1 in the cerebral cortex, especially in the affected cortex, increased the content of Rg1 in the healthy and the affected cortex, and increased the content of notoginsenoside R1 in the cerebral cortex, especially in the affected cortex, as well as in the cerebellum. Conclusion AST IV and the bioactive components of PNS such as ginsenoside Rg1, ginsenoside Rb1, and notoginsenoside R1 have a certain distribution in the cerebral cortex and the cerebellum after cerebral ischemia-reperfusion in rats. AST IV was mainly distributed in the cerebral cortex when it was used alone, ginsenoside Rg1, ginsenoside Rb1, and notoginsenoside R1 were mainly distributed in the cerebellum when PNS was used alone. The combination of borneol combined with AST IV and PNS can promote the gather of AST IV, ginsenoside Rg1, ginsenoside Rb1, and notoginsenoside R1 to the cerebral cortex, especially to the cortex of the ischemia-reperfusion side; Moreover, it can promote the absorption of AST IV, ginsenoside Rg1, ginsenoside Rb1, and notoginsenoside R1 in the cerebral cortex to varying degrees, especially in the affected cortex.

Research Advance in the Drug Absorption Model of Vaginal Administration / 中国药师

Vaginal delivery system has a unique therapeutic advantage. In recent years, the rapid development of dosage forms shows a good prospect of development. The related literatures at home and abroad in recent years were analyzed and summarized. The research progress in the drug absorption model of various vaginal administrations was reviewed. The review provided reference for the research of new drug preparations and drug absorption mechanisms of vaginal administration.

Effect of lipid and surfactant digestion on poorly water-soluble drug solubilization and absorption in gastrointestinal tract using self-emulsifying drug delivery systems / 国际药学研究杂志

Self-emulsifying drug delivery systems (SEDDS) are a vital tool in solving low oral bioavailability of poorly soluble drugs (PWSD). SEDDS may improve oral absorption via several mechanisms, however, enhancement of gastrointestinal solubilization of PWSD remains the most important factor of absorption enhancement. This review introduces the methods including dispersion tests and lipolysis tests in vitro as the indicators of potential performance in vivo. The use of these methods in vitro combined with oral bioavailability study is subsequently described, with particular focus on recent data which suggest that the digestion of lipid and surfactants present in SEDDS formulations impact on formulation performance in vivo. This review is expected to provide some guiding principles on formulation design of SEDDS.

Effect of lipid and surfactant digestion on poorly water-soluble drug solubilization and absorption in gastrointestinal tract using self-emulsifying drug delivery systems / 国际药学研究杂志

Self-emulsifying drug delivery systems(SEDDS)are a vital tool in solving low oral bioavailability of poorly soluble drugs(PWSD). SEDDS may improve oral absorption via several mechanisms,however,enhancement of gastrointestinal solubilization of PWSD remains the most important factor of absorption enhancement. This review introduces the methods including dispersion tests and lipolysis tests in vitro as the indicators of potential performance in vivo. The use of these methods in vitro combined with oral bio?availability study is subsequently described,with particular focus on recent data which suggest that the digestion of lipid and surfac?tants present in SEDDS formulations impact on formulation performance in vivo. This review is expected to provide some guiding princi?ples on formulation design of SEDDS.

The research of mesoporous silica nanoparticles MCM-41 loading ginsenoside Rg3 for human lung cancer cells A549 / 中国药学杂志

OBJECTIVE: To improve the water solubility of ginsenoside Rg3, using mesoporous silica nanoparticles MCM-41 loading ginsenoside Rg3 and study the mechanism of promoting drug absorption with human lung cancer cells A549 as a model. METHODS: The mesoporous silica nanoparticles MCM-41, as a carrier, loading ginsenoside Rg3 by adsorption method. The morphology and particle size of MCM-41 were investigated by transmission electron microscopy (TEM) and laser particle size analyzer. The solid state characterization of ginsenoside Rg3 were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy method (FTIR), respectively. In vitro dissolution experiments investigated the dissolution rate of ginsenoside Rg3. Cytotoxicity assay and cell uptake experiments explored the effect of the administration system of A549 cells and the mechanism of inhibiting cell proliferation. RESULTS: We have been successfully prepared the mesoporous silica nanoparticles MCM-41. In vitro dissolution experiments showed that MCM-41 can significantly improve the dissolution rates of ginsenoside Rg3. Administration system can be uptaked into A549 cells and inhibit cell proliferation. CONCLUSION: The mesoporous silica nanoparticles MCM-41 has a good solubilization effect for ginsenoside Rg3, and MCM-41 has potential as a carrier for the treatment of lung cancer.

A Study Investigating the Absorption and Pharmacokinetics of a Newly Developed Paracetamol/Caffeine Formulation Containing Sodium Bicarbonate in Healthy Volunteers.

Aims: To assess pharmacokinetic (PK) bioequivalence between a newly developed formulation, rapid-relese paracetamol plus sodium bicarbonate and caffeine (RAPC), containing 500 mg paracetamol + 65 mg caffeine + 325 mg sodium bicarbonate), and the currently marketed Panadol® Extra product in both the fasted and semi-fed states. Study Design: A single center, randomized, open label, four-way crossover, PK study. Place and Duration of Study: MDS Pharma Services (Now Celerion), 2420, W. Baseline Road, Tempe, AZ 85283, between July 17, 2009 to August 10, 2009. Methodology: We included 30 healthy volunteers (20 males, 10 females; age range 18- 55 years). The characterized PK parameters included total and partial area under the concentration time curve (AUC0-30min, AUC0-60min, AUC0-t/AUC0-∞), time to reach peak drug plasma concentration/therapeutic level (Tmax/Tc≥4ug/ml), and maximum measured plasma concentration (Cmax). The safety of the study treatments was also assessed. Results: In both fasted and semi-fed states, the exposure to paracetamol and caffeine for new RAPC formulation was bioequivalent to Panadol® Extra for AUC0-10 hrs, AUC0-∞ and Cmax with 90% confidence intervals (CIs), all being within the range 0.80 to 1.25, except for a higher paracetamol Cmax for RAPC in fasted state. RAPC exhibited significantly greater early absorption for both paracetamol (≥1.8-fold greater) and caffeine (≥1.3-fold greater) as determined by AUC0-30min and AUC0-60min, as well as significantly faster Tmax for both paracetamol (about 30 minutes faster) and caffeine (≥15 minutes faster) compared to currently marketed Panadol® Extra in both fasted and semi-fed states. The time to reach the therapeutic paracetamol plasma concentration (Tc≥4μg/ml) was about 12 and 33 minutes faster in fasted and semi-fed states respectively. The new formulation was safe and well tolerated. Conclusion: The newly developed RAPC formulation was found to be bioequivalent to Panadol® Extra caplets, and showed significantly faster absorption in both fasted and semi-fed states.

In Vitro and In Vivo Evaluation of Combined Time and pH- Dependent Oral Colonic Targeted Prednisolone Microspheres.

Aims: to enhance the anti-inflammatory effect as well as oral absorption of prednisolone (PR), through formulation of colonic targeted microspheres prepared from a blend of time and pH- dependent polymers and loaded with PR. Study Design: In Vitro and In Vivo Evaluation of Combined Time and pH- Dependent Oral Colonic Targeted Prednisolone Microspheres. Place and Duration of Study: Department of Pharmaceutics and Industrial Pharmacy, Helwan University, Cairo, Egypt between June 2011 and October 2012. Methodology: Microspheres were prepared by solvent evaporation method using different ethyl cellulose (EC) and Eudragit® S-100 (ES100) ratios with 0.5 and 1% w/v span® 80 as emulsifier. The microspheres were evaluated for surface morphology, particle size, drug encapsulation efficiency % and in vitro drug release at pH 1.2 and 7.4. The antiinflammatory activity of selected formula was compared to that of conventional PR tablets. Results: A decrease in drug entrapment efficiency % was obtained with increasing both polymers and surfactant concentrations. Based on drug release results, the formula of 1: 1: 0.16 w/w/w, EC: ES100: PR ratio with 1% w/v span® 80 was selected for further histopathological evaluation of the anti-inflammatory activity in colitis induced-rats. Histopathological study showed undefined tissue necrosis after treatment with the selected microspheres; however, diffused necrosis was observed in rats treated with the commercial tablets. In vivo absorption study showed that values of Cmax and AUC0-24 of both formulations were insignificantly different. However, the occurrence of Cmax of microspheres was significantly delayed in comparison to free drug (9.17 to 2.67hr) (P<.001). Conclusion: This study has supplied us with brightening results concerning the therapeutic efficacy of a blend of time and pH- dependent polymers colonic targeted microspheres.

A review on intestinal lymphatic drug transport / 中国药学杂志

OBJECTIVE: Available information on the background of the current state and advances of the intestinal lymph trans port of medicines were reviewed. Drug transported by the intestinal lymphatic system can avoid hepatic first-pass metabolism, increase the bioavalibitlty of the highly lipophilic drug, and it is of importance for immunomodulatory, anticancer and anti-infective drugs. METHODS: We conducted a systematic literature review of articles published recent years, analysis and summaries are made upon the advances and methods applied for the increase of the intestinal lymph transport. RESULTS AND CONCLUSION: Intestinal lymphatic transport can increase the bioavailability via a reduction in the first-pass metabolism and the possibility of specifically targeting drugs to regions of the lymphatics, thus it is very advantageous for drugs that are under significant first-pass metabolism. The present review embodies a brief background of the mechanism of access of drugs to the intestinal lymph, a discussion on the links between lipid absorption and transport of highly lipophilic drugs, and approaches for enhancing lymphatic drug transport. Finally, experimental models of the lymphatic transport are also discussed.

Sublingual drug dispensing prosthesis.

Sublingual mode of drug administration is one of the fastest and predictable methods of drug delivery to the patient. Some patients, due to the pathological or psychological reasons, experience considerable difficulty in retaining the sub-lingual tablets. Therefore, often they either swallow or chew the sublingual tablets, thus reducing the efficacy of the medicines. Sublingual drug dispensing prosthesis is a special type of appliance that helps such patients to house the sublingual tablets in special slots in an intra-oral appliance, and thus enhances proposed drug delivery and improves the patient's health.

Study on factors influencing on degree of stability and drug absorption of diclofenac sodium injection

Study on white sewer- rat. Result: stable degree of injection solution Ned 2,5% depend on propylen glycol rate in sloven mixture used to compound drug, pH of solution, type of antioxygen agent, antioxygen agent level, agent of cooperate against oxygen and high of propylen glycol and pH in injection solution level.

Study on in vitro models of drug absorption / 中国临床药理学与治疗学

This article summarized some in vitro models of drug absorption,whose shortcomings and virtues were compared in order to be convenient for researchers to know and select optimal model.

Caco-2 cell model——an effective tool for the research of drug absorption / 中国药理学通报

The absorption process is an important factor in determining the bioavailability of orally administered drugs. however, the absorption mechanism of many drugs is not clear. Caco-2 cell model is the best in vitro absorption model nowadays. It is widely used in the research on drug absorption process and absorption mechanism, especially in the aspect of traditional Chinese medicine absorption, the use of Caco-2 cell model has become the hot spot recently. Mo- reover, Caco-2 cell model is also applied in the research on drug metabolism. Therefore, Caco-2 cell model will become an important method in the research of drug absorption, and will be helpful to accelerate the process of new drug screening and development.