Pharmacokinetics and in vitro-in vivo correlation of progesterone suspension injection / 中国药科大学学报

@#Abstract: To investigate the in vitro release, in vivo pharmacokinetics, and the in vitro-in vivo correlation of progesterone suspension injection, self-made progesterone suspension injection was taken as an example. The in vitro release curves of three different particle sizes of progesterone suspension injections were measured using paddle method and dialysis bag method. The in vivo pharmacokinetic characteristics of self-made progesterone suspension injection was studied on SD rats. The plasma concentration of self-made progesterone preparation was detected after intramuscular injection, and correlated with the in vitro release profiles obtained by the dialysis bag method after processing by Wagner-Nelson method. The results showed that when the in vitro release of three different particle sizes of progesterone suspension injections was measured by the paddle method, more than 85% was rapidly released within 20 min, while 85% cumulative release was reached at 40 h, 84 h and 120 h by dialysis bag method, respectively. The release rate obtained by the dialysis bag method was basically consistent with the in vivo release trend, with a correlation coefficient of >0.95, indicating a strong in vivo and in vitro correlation. This study provides some reference for the establishment of the in vitro and in vivo correlation of long-acting suspension injection.

Blaps rynchopetera affects proliferation, migration, and invasion of non-small cell lung cancer: a study based on network pharmacology and in vivo and in vitro experiments / 中国中药杂志

Network pharmacology, molecular docking, and in vivo and in vitro experiments were employed to study the molecular mechanism of Blaps rynchopetera Fairmaire in the treatment of non-small cell lung cancer(NSCLC). The components of B. rynchopetera were collected by literature review, and the active components were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). PharmMapper was used to obtain the targets of the active components. The targets of NSCLC were obtained from DrugBank, GeneCards, OMIM, TTD, and PharmGKB. The Venn diagram was drawn to identify the common targets shared by the active components of B. rynchopetera and NSCLC. The "drug component-target" network and protein-protein interaction(PPI) network were constructed by Cytoscape, and the key targets were screened by Centiscape. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the above key targets were performed by DAVID. AutoDock and PyMOL were used for the molecular docking between the key targets and corresponding active components. A total of 31 active components, 72 potential targets, and 11 key targets of B. rynchopetera against NSCLC were obtained. The active components of B. rynchopetera had good binding activity with key targets. Further, the serum containing B. rynchopetera was prepared and used to culture human lung adenocarcinoma A549 cells. The CCK-8 assay was employed to determine the inhibition rates on the growth of A549 cells in blank control group and those exposed to different concentrations of B. rynchopetera-containing serum, cisplatin, and drug combination(B. rynchopetera-containing serum+cisplatin) for different time periods. The cell migration and invasion of A549 cells were detected by cell scratch assay and Transwell assay, respectively. Western blot was employed to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), caspase-3, cell division cycle 42(CDC42), proto-oncogene tyrosine-protein kinase SRC, and vascular endothelial growth factor(VEGF) in A549 cells. C57BL/6 mice were inoculated with Lewis cells and randomly assigned into a model control group, a B. rynchopetera group, a cisplatin group, and a drug combination(B. rynchopetera+cisplatin) group, with 12 mice per group. The body weight and the long diameter(a) and short diameter(b) of the tumor were monitored every other day during treatment, and the tumor volume(mm~3) was calculated as 0.52ab~2. After 14 days of continuous medication, the mice were sacrificed for the collection of tumor, spleen, and thymus, and the tumor inhibition rate and immune organ indexes were calculated. The tissue morphology of tumors was observed by hematoxylin-eosin(HE) staining, and the positive expression of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF in the tumor tissue was detected by immunohistochemistry. The results indicated that B. rynchopetera and the drug combination regulated the expression levels of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF to inhibit the proliferation, migration, and invasion of A549 cells and Lewis cells, thus playing a role in the treatment of NSCLC via multiple ways.

Advances in approved nucleic acid drugs and lipid nanoparticle system / 药学学报

Nucleic acids, as a next generation of biotechnology drugs, not only can fundamentally treat diseases, but also own significant platform characteristics in view of technology and production. Therefore, nucleic acid-based drugs have broad clinical applications in biomedical fields. However, nucleic acids are degradable and unstable, and have very low intracellular delivery efficiency in vitro and in vivo, which greatly limits their applications. In recent years, ionizable lipid-based lipid nanoparticles have shown promising application potentials and have been successfully applied to COVID-19 (Coronavirus Disease 2019) vaccines in clinic. Lipid nanoparticles demonstrate high in vivo delivery efficiency and good safety profile due to their unique structural and physicochemical properties, which provides many possibilities for their clinical applications for nucleic acid delivery in the future. This review focused on the characteristics of nucleic acid drugs and their delivery barriers, and discussed the approved nucleic acid drugs to illustrate the key aspects of the success of their delivery carrier system. In addition, problems to be solved in the field were highlighted.

In-vitro and in-vivo evaluation of the antibacterial potential of Typha elephantina

@#The present study was aimed to evaluate the in-vitro and in-vivo antibacterial effects of the Typha elephantina aqueous extract (TE.AQ), ethanolic extract (TE.ET) and T. elephantina methanolic extract (TE.ME) against eight selected clinical pathogens. The test samples were tested for in-vitro analysis (by disc diffusion method) at different concentrations of 5, 15, 25, 50 and 100 mg/dL against both gram positive and gram-negative strains. The highest potential was observed in TE.ME at a concentration of 100 mg/dL against Pseudomonas aeruginosa exhibiting 19.67 ± 0.577 mm zone of inhibition (ZOI). The same fraction also showed good activity against Staphylococus aureus with ZOI of 17.50 ± 0.70 mm. The TE.ET was found most active against P. aeruginosa and Streptococcus pyogenes having ZOI of 18.53 ± 0.503 and 16.2 ± 1.55 mm respectively at a concentration of 100 mg/dL. The most sensitive bacteria P. aeruginosa was selected for in-vivo study (using poultry chicks) for induction of infection in chicks. The effects of TE.AQ, TE.ET and TE.ME were determined at concentrations of 300 mg/kg body weight based on hematological parameters, liver enzymes and gross pathological findings of lungs and livers. The findings of the in-vivo study in chick’s model showed that treatment of experimental animals with TE.ME significantly restored the hematological parameters, liver enzymes and architecture of lungs and livers. Based on scientific evidence, the current study suggests that TE.ME may serve as a best and new natural antibacterial agent and can be used against infections caused by P. aeruginosa.

Elevated Iron Chelating Activity of Ilex paraguariensis Leaf Infusion: in vitro and in vivo Pilot Studies

Abstract This study presents an Ilex paraguariensis leaf infusion with important potential as natural iron-chelating. The impact of infusion time and the water volume to obtain an Ilex paraguariensis leaf infusion with high phenolic content and iron chelating activity, such as the stability of these proprieties in the storage time and temperature (immediately and after 24 h at 8 and 25 (C) were assessed. The acute consumption effect of this infusion to reduce iron absorption in vivo was also evaluated. A preliminary crossover trial with volunteers that ingested a meal containing non-haem iron (11.4 mg) with the treatments: Ilex paraguariensis leaf infusion with the highest phenolic content and iron chelating activity (200 mL) or control (200 mL water). Blood samples were withdrawn before and 1, 2, 3 and 4 h after the meal for serum iron measurement. The highest phenolic content (18.1 mg/mL) and iron chelating activity ((100%) were observed for 10 min infusion time using 30 g leaves/300 mL water. Storage at 8 or 25 (C for 24 h decreased total phenolics and di-caffeoylquinic acids by 23.5% and 25.5%, respectively (p< 0.05), without affecting the iron-chelating activity due to a saturating chelating effect at 3.34 mg/mL phenolic content. Inhibition of the iron absorption in vivo by infusion was 78% considering the iron recovery at peak maximum. The in vitro and preliminary in vivo results showed a functional property of the Ilex paraguariensis leaf infusion that may be useful for adjuvant management of iron overload diseases.

Overview of Experimental Methods for Antimicrobial Activity of Natural Drugs / 中国实验方剂学杂志

The antibiotics have obvious antibacterial and anti-inflammatory effects, but their toxic side effect, secondary infection and bacterial resistance have become a global problem. Traditional Chinese medicine(TCM) has always been the treasure of traditional culture and national characteristics in China since ancient times. It also has remarkable effect on inhibiting the growth of bacteria and killing pathogenic bacteria. The research on bacteriostatic experiment of TCM has gradually become a hot topic. Sensitivity experiments for such natural medicines have gradually become a research hotspot, but the complexity and particularity of natural medicines will vary with different methods. Therefore, different methods of drug sensitivity experiments should be matched with different natural drugs. By collecting and sorting out the relevant literature at home and abroad, this paper systematically summarizes the commonly used in vitro, in vivo and their combination bacteriostasis experimental methods of natural medicine activity, analyses the advantages and disadvantages of each method in the process of application, finds that different kinds of natural drugs have different applicable methods, and puts forward suggestions for the operation of each experimental method, in order to provide ideas for the selection of antibacterial susceptibility research experiments of natural medicines. It also provides a reliable reference method for solving the problem of antibiotic abuse and the development and utilization of natural medicines.

Research Progress of Vaginal Mucosal Drug Delivery System / 中国实验方剂学杂志

Because it can not only directly reach the lesion site to play a local therapeutic effect, but also avoid the liver first pass effect and play a systemic therapeutic effect, vaginal mucosal administration has attracted more and more attention from domestic and foreign scholars in the treatment of vaginitis, cervicitis and other diseases. This article introduces the physiological characteristics of the vagina and discusses the factors affecting drug absorption. The vaginal mucosal drug-administered preparations, which are contained in the drug database of U.S. Food and Drug Administration(FDA) and China Food and Drug Administration(CFDA), and listed in the 2015 edition of Chinese Pharmacopoeia, are taken as the research objects. And the application of their dosage forms, indications and other aspects were sorted out and analyzed. The related literature on vaginal mucosal drug delivery systems in recent years was reviewed, and the dosages forms and in vitro and in vivo evaluation were summarized. Some problems in the study of vaginal mucosal drug preparations have been pointed out:①the western medicine preparations are widely used, and the related Chinese medicine preparations have been developed less; ②the majority of dosage forms are tablets, suppositories and other conventional dosage forms; ③there are few studies on the evaluation of vaginal mucosal preparations in vitro and in vivo. It is suggested that the future development of vaginal mucosal drug delivery system can be a useful attempt in the application of new technologies and methods, such as combination of drugs, high adhesion excipients, liposomes, etc;so as to provide reference for the application and improvement of vaginal mucosal drug delivery system.

A new method based on flow-through cell apparatus to evaluate dissolution consistency of nimodipine tablets / 中国药科大学学报

A new method of dissolution test was established to better simulate the in vivo dissolution behavior of drugs from preparations and to distinguish the quality difference between drug preparations. With flow-through cell being chosen to be the dissolution apparatus and nimodipine tablet to be the model drugs,this study developed,on the basis of IVIVC theory,a new dissolution method which was subsequently used to evaluate the dissolution con-sistency of domestically produced nimodipine tablet as test preparation and its reference preparation. Meanwhile, conventional four-dissolution-curves method based on paddle apparatus was selected for comparison to evaluate the efficiency of the new dissolution method. The results indicated that the new dissolution method not only had a good correlation with the in vivo process of drugs,but also could reveal the internal quality differences between pharmaceutical preparations effectively. This research will provide further theoretical support for the application of flow-through cell apparatus in IVIVC study.

Discussion of development and validation of dissolution methods for solid oral dosage forms / 药学学报

It is generally assumed that study of in vitro dissolution can reveal the in vivo behavior and bioavailability of a drug. The dissolution test indisputably plays a vital role in the research and development of pharmaceutical preparations as well as routine quality control of approved drugs. In order to develop an ideal dissolution method, the physicochemical properties of drug and the characteristics of its dosage form should be considered, and a proper dissolution condition be established to simulate the in vivo dissolution behavior of drugs. The new dissolution method should have the required characteristics of accuracy and durability, but also could distinguish pharmaceutic preparations with different quality. In recent years, there have been more and more reports on the establishment and verification of dissolution methods for oral solid dosage forms. However, there is very few review articles on the topic. According to the latest guidelines by domestic and foreign drug organizations, this review paper is prepared to summarize the most important skills and progress in the development of dissolution methods for oral solid preparations. The aim is to provide a reference for the development and validation of new dissolution methods.

In vivo and in vitro correlation of azithromycin cationic micron niosomes / 中国药理学通报

Aim To evaluate the correlation between in vitro release and in vivo absorption of azithromycin cat-ionic micron niosomes (ACMNS)by Wagner-Nelson method and deconvolution method. Methods The in vitro release behavior of ACMNS was studied by dy-namic membrane dialysis. After a single dose of intra-gastric administration with ACMNS and AM in rats,the AM concentrations in plasma were determined by high performance liquid chromatography(HPLC). Wagner-Nelson and deconvolution method were used to reveal the in vitro / in vivo correlation. Results X used as cu-mulative in vitro release and Fa as the absorption per-centage,the regression equation was established:F a =3. 0524X - 5. 7709,r = 0. 8976,and X used as cumu-lative in vitro release and R as input function,the re-gression equation was established:R = 2. 3413X -58. 687,r = 0. 5217. r < r( 2,0. 05) = 0. 9500 (P <0. 05). Conclusion There is no correlation between in vitro release and in vivo absorption of ACMNS.

Experimental study on herpetrione nanosuspension against hepatitis B virus in Vitro and in Vivo / 中国药学杂志

OBJECTIVE: To evaluate the anti-hepatitis B virus (HBV) activity of herpetrione nanosuspension (PEDX-NS) both in vitro and in vivo. METHODS: HepG2 2.2.15 cells and duck hepatitis B virus (DHBV) infected ducks as in vitro and in vivo models were used to compare the anti-HBV activity of PEDX-NS and PEDX coarse suspension (PEDX-CS). RESULTS: In the HepG2 2.2.15 cell, PEDX-NS effectively suppressed the secretion of the HBV antigens (HBsAg and HBeAg) in a dose-dependent manner with significant difference from PEDX-CS (P<0.05 or P<0.01). In the in vivo evaluation, PEDX-NS with high dose (100 mg·kg-1) and middle dose (60 mg·kg-1) significantly reduced the serum HBV DNA level (P<0.05 or P<0.01) and the effect was better than that of PEDX-CS (P<0.05 or P<0.01). CONCLUSION: The result revealed that PEDX-NS exhibits anti-HBV activity both in vitro and in vivo and its effect was superior to that of PEDX-CS. The mechanism is probably that the small particle size of PEDX-NS provides a large specific surface area that resulted in better absorption in vivo, thus enhancing its anti-HBV activity.

In vitro and In vivo Antitrypanosomal Effects of Petroleum Ether, Chloroform and Methanol Extracts of Artemisia maritima Linn.

Petroleum ether, chloroform and methanol extracts of the whole plant of Artemisia maritima Linn were studied in vitro and in vivo for antitrypanosomal activity against Trypanosoma brucei brucei in Swiss albino mice. The extracts were also screened for phytochemicals/secondary metabolites. All the extracts showed trypanocidal activity against T. brucei brucei in vitro with the petroleum ether extract showing the highest activity. The in vivo study revealed that only the chloroform extract A. maritima exhibited antitrypanosomal activity. This extract at a dose of 100mg/kg body weight significantly (p<0.05) reduced the parasitemia in T. brucei brucei infected mice when compared with the other treatment groups. The chloroform extract of A. maritima at this dose reduced the level of parasitemia to 26%. This reduction in the level of parasitemia is statistically significant (p<0.05) compared to the other treatment groups and the untreated control group. The result of the phytochemical analysis revealed that the extracts contain secondary metabolites like flavonoids, terpenoids, steroids, anthraquinones and alkaloids. The presence of these secondary metabolites in this plant might be responsible for the antitrypanosomal activity exhibited by its extracts.

In vitro and in vivo Antitrypanosomal Effects of Methanol and Aqueous Extracts of Picralima nitida.

The methanol and aqueous extracts of the leaves, fruits, seeds, stem bark and roots of Picralima nitida were studied in vitro and in vivo for activity against Trypanosoma brucei brucei in Swiss albino mice. Phytochemicals studies were also conducted for all the plant extracts. The methanol extracts showed appreciably high in vitro and in vivo antitrypanosomal activities compared to the aqueous extracts of the plant. The methanol extract of the root exhibited the highest in vitro antitrypanosomal activity followed by the methanol extract of seed of Picralima nitida. Motility of Trypanosoma brucei brucei was stopped by the methanol extract of the root after 10 min, while the methanol extract of the seed of Picralima nitida stopped the motility of Trypanosoma brucei brucei at 15 min. The methanol extract of the root of Picralima nitida showed the highest in vivo antitrypanosomal activity at 100 mg/kg body weight. The extract cleared the parasite completely from the T. brucei brucei infected Swiss albino mice after day 3 of treatment. There was a statistically significant difference (p<0.05) when the level of parasitemia of the animals treated with the methanol extract of the root of Picralima nitida were compared with the other treatment groups and the untreated control. The phytochemicals detected in these extracts are tannins, flavonoids, alkaloids, steroids, terpenoids, saponins and cyanide glycosides. The in vitro and in vivo antitrypanosomal activity exhibited by these extracts might be attributed to these phytochemicals.

In vitro and in vivo antioxidant properties of the total flavonoids from Lithocarpus polystachyus Rehd / 中国药学杂志

OBJECTIVE: To examine the antioxidant properties of the total flavonoids from Lithocarpus polystachyus Rehd (TFL) in vitro and in vivo. METHODS: The TFL was obtained by ultrasound-assisted extraction with 70% ethanol and purified with D-101 macroreticular resin. DPPH, ABTS, reducing power and ORAC of TFL were analyzed for antioxidant activity in vitro, with VC and rutin as control. Acute liver injury mice model was induced with carbon tetrachloride (CCl4), the effect of TFL on the superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) levels were examined. RESULT: At 1 mg·mL-1 of TFL, the DPPH and ABTS radicals-scavenging activities was 81.25% and 85.54% respectively, while the reducing power was slightly lower than that of VC but higher than that of rutin. In the concentration of 1%, 2% and 3%, the value of ORAC was 47.86, 65.43 and 81.9 μmol TE·g-1 respectively. In mice with CCl4-induced actute liver injury model, TFL at the concentration of 100, 200 and 400 mg·mL-1 significantly decreased the MDA content, and increased the activities of SOD, CAT and GSH. CONCLUSION: The total flavonoids from Lithocarpus polystachyus Rehd. have a strong antioxidant effect.

Antioxidative effect of rhodiola granules in vitro and in vivo / 中国药学杂志

METHODS: Female Kunming mice were randomly divided into five groups, ie, blank control group, low-dose group, middle-dose group, high-dose group, and the positive control group. The three treatment groups were given various doses of Rhodiola granules, ie, 0. 1, 1, 3 g��kg-1 respectively, the positive control group were given Nuodikang capsules at 280 mg��kg-1, and the blank control group was given deionized water for 35 d. The levels of SOD, MDA, GSH-PX in serum, liver, and brain were determined. For the experiment in vitro, with vitamin C as the control drug, the absorbance of Rhodiola granule solution at concentrations of 0.01, 0.1, 1, 10 mg��mL-1 was measured, and the activity of scavenging superoxide anion free radicals and hydroxyl free radicals was calculated.

Evaluation of cytotoxicity and mutagenicity of the benzodiazepine flunitrazepam in vitro and in vivo

Flunitrazepam (FNZ) is a sedative benzodiazepine prescribed for the short-term treatment of insomnia. However, there are concerns regarding possible carcinogenic or genotoxic effects of this medicine. Thus, the aim of this study was to evaluate the cytotoxic, clastogenic and aneugenic effects of FNZ in hepatoma cells from Rattus norvegicus (HTC) in vitro and in bone marrow cells of Wistar rats in vivo. These effects were examined in vitro following treatment with 0.2, 1.0, 5.0 or 10 μg/mL FNZ using a micronucleus test with a cytokinesis block or in vivo using a chromosomal aberration test following treatment with 7, 15 or 30 μg/mL/kg body weight. The results showed that the benzodiazepine concentrations tested were not cytotoxic, aneugenic or clastogenic. However, considering the adverse effects of using this benzodiazepine, more studies are required.

Flunitrazepam (FNZ) é um sedativo benzodiazepínico prescrito para o tratamento da insônia em curto prazo. Entretanto, existe a preocupação com relação aos possíveis efeitos carcinogênicos ou genotóxicos causados por este fármaco. Então, o objetivo deste estudo foi avaliar os efeitos citotóxicos, clastogênicos e aneugênicos do FNZ em células de hepatoma de Rattus norvegicus (HTC) in vitro e em células de medula óssea de ratos Wistar in vivo. Foram testadas as concentrações de 0,2, 1,0 e 10 μg/mL de FNZ pelo teste do micronúcleo com bloqueio de citocinese in vitro e 7, 15 e 30 μg/mL/kg de peso corpóreo para o teste de aberração cromossômica in vivo. Os resultados mostraram que as concentrações do benzodiazepínico testadas não foram citotóxicas, aneugênicas ou clastogênicas. Entretanto, considerando os efeitos adversos do uso deste benzodiazepínico, mais estudos são necessários.

Potential of immunosuppressive agents in cerebral ischaemia.

Ischaemic stroke is a disorder involving multiple mechanisms of injury progression including activation of glutamate receptors, release of proinflammatory cytokines, nitric oxide (NO), free oxygen radicals and proteases. Presently, recombinant tissue plasminogen activator (rtPA) is the only drug approved for the management of acute ischaemic stroke. This drug, however, is associated with limitations like narrow therapeutic window and increased risk of intracranial haemorrhage. A large number of therapeutic agents have been tested including N-methly-D-aspartate (NMDA) receptor antagonist, calcium channel blockers and antioxidants for management of stroke, but none has provided significant neuroprotection in clinical trials. Therefore, searching for other potentially effective drugs for ischaemic stroke management becomes important. Immunosuppressive agents with their wide array of mechanisms have potential as neuroprotectants. Corticosteroids, immunophilin ligands, mycophenolate mofetil and minocycline have shown protective effect on neurons by their direct actions or attenuating toxic effects of mediators of inflammation. This review focuses on the current status of corticosteroids, cyclosporine A, FK506, rapamycin, mycophenolate mofetil and minocycline in the experimental models of cerebral ischaemia.

Coeficiente de ultrafiltración en dializadores de bajo y alto flujo reusados / Coefficient of ultrafiltration in reused low and high flow dialyzers

El reúso de los dializadores constituye un problema de gran magnitud en nuestro país. Se realizó un estudio observacional, descriptivo, prospectivo para determinar el Kuf de los dializadores de BF y AF reusados. Se estudiaron 8 pacientes en el Servicio de Hemodiálisis del Instituto de Nefrología Dr Abelardo Buch López, durante 18 sem, se utilizaron membranas de BF y AF, durante 2 etapas. El reúso fue automatizado, utilizando como germicida ácido peracético. Se midió Kuf in vitro e in vivo durante todas las hemodiálisis, se realizaron 432 hemodiálisis. El Kuf in vitro e in vivo de ambos tipos de dializadores disminuyó considerablemente en los primeros 6 usos. El Kuf de ambos tipos de dializadores tiene una importante disminución con el reprocesamiento.

Reuse of dialyzers is a serious problem in our country. To perform an observational, descriptive and prospective study to determine the Kuf of reused low-flow (LF) and high-flow (HF) dialyzers. Eight patients were studied in Hemodialysis Service of Dr Abelardo Buch López Nephrology Institute during 18 weeks, using LF and HL membranes in two stages. Reuse was automated using peracetic. acid like germicide. In vitro and in vivo Kuf was measured during all Hemodialysis (431 in total). In vitro and in vivo Kuf of both types of dialyzers decrease significantly during the first six uses. Kuf of both types of dialyzers has an important diminution with re-processing.

Pharmacokinetics and in vitro-in vivo correlation evaluation of self-emulsifying drug delivery system and conventional tablets of aniracetam / 中国临床药理学与治疗学

AIM: To evaluate the correlation between in vitro release and in vivo absorption of aniracetam in conventional tablets and self-emulsifying drug delivery system (SEDDS), to investigate pharmacokinetics of aniracetam self-emulsifying drug delivery system and conventional tablets of aniracetam after oral administration to rats. METHODS: Dissolution behavior of these formulations was evaluated in vitro to assess the properties of dosage forms. And a new RP-HPLC method was developed for the in vivo quantitative determination of 4-p-anisamidobutyric acid (PABA), the active metabolite of aniracetam. To approach the in vitro-in vivo correlation, fraction absorbed in vivo (f) was calculated by Wagner-Nelson method, and then compared with in vitro released drug percentages (Q%). RESULTS: Aniracetam was released rapidly from SEDDS with 80%±4% of accumulation dissolution rate compared to that from conventional tablets at 15 min. The recovery of active metabolite of aniracetam was about 90%, and the intra-days and inter-day precision were within 4% and 6%, respectively. The AUC0-∞ value of aniracetam SEDDS was (11 168±2 395) ng·mL-1·h, which was about 3 folds greater than conventional tablets. The parameter MRT0-∞ of aniracetam SEDDS and conventional tablets were (2.7±0.6) h and (1.7±0.6) h, respectively, and the difference was statistically significant(P<0.05). The linear equation of in vitro-in vivo correlation for conventional tablets was obtained by regression as well. Whereas nonlinear correlation was obtained for aniracetam SEDDS, which fitted the quadric model very well and the correlation coefficient was 0.972. CONCLUSION: Aniracetam can be released faster from SEDDS than that from conventional tablets, and SEDDS improved the bioavailability of aniracetam significantly. The SEDDS composed by oil and compound surfactants which could enhance the absorption showed the expressing rate of dissolution, and those formed the o/w microemulsion with gastrointestinal liquid could absorb through lymphatic transport route.

Preparation of Growth Hormone-Chitosan-Alginate Microcapsules and the Release Profile / 医学研究杂志

Objective To study the preparation and the in vitro and in vivo release profile of GH-Chitosan-Alginate microcapsules.Methods GH-Chitosan-Alginate microcapsules were prepared through impulsive electrostatic technique.The interrelated factors influencing the diameter and sphericity were studied through orthogonal experiments,and finally the statistic analysis made sure the optimum conditions to prepare microspheres.The morphology and size of the microcapsules were observed,and the content,encapsulation efficiency and recovery efficiency of the microcapsules were measured.Moreover,their in vitro and in vivo release experiments were carried out.Results The results showed that the diameter of needle was the most significant factor to the diameter of microspheres.The optimum conditions for the least diameter of microspheres were 450?m diameter of needle,2cm from needle tips to the gelation surfaee,1.5% alginate concentration,8ml/h speed of flowing-liquid and metal containers.The microcapsules had good sphericity morphology and distribution.The size of the microcapsules was in the range of 10-25?m with an average size of 47.93?m.The encapsulation efficiency and GH-load of the microcapsules were 94% and 11.24% respectively.The release kinetics of microcapsules was studied in false gastric and intestines juice.In false gastric juice,the GH of microcapsules was not released;in false intestines juice,it was released well,and TAM was completely released after about 12h.in vivo release profile made sure that the serum GH level of GH microcapsule group was at the highest value(98.59ng/ml) at 8h.The release profile was fitted well in both in vitro and in vivo conditions.Conclusion GH-Chitosan-Alginate Microcapsules have good morphology and sustained release effect.